Isotopically-stabilized tetronimide compounds

ABSTRACT

Isotopically-stabilized tetronimide compounds comprising one or more deuterium atoms, derivatives, and intermediates, thereof, including methods for their synthesis, pharmaceutical compositions thereof, and methods of using these compounds to interact with target molecules in cell-free samples, cell- and tissue-based assays, animal models, and in a subject are disclosed. One aspect relates to molecules that modulate the expression or catalytic activity of aspartyl (asparaginyl) β-hydroxylase (ASPH) within or on the surface of a cell. Other aspects of the invention relate to use of the molecules disclosed herein to diagnose, ameliorate, or treat cell proliferation disorders and related diseases. Related aspects include uses of the compounds to modulate the activity of viruses, as anti-hyperlipidemia agents, and as agents to ameliorate or treat thrombosis and related cardiovascular and metabolic disorders.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority to and the benefit of U.S. ProvisionalApplication No. 62/806,327, filed Feb. 15, 2019, the entire contents ofwhich are incorporated by reference in their entirety.

INCORPORATION-BY-REFERENCE OF A SEQUENCE LISTING

The sequence listing contained in the files“761_190_030_US_02_Sequence_Listing_ST25.txt”, created on 2020 Feb. 21,modified on 2020 Feb. 21, file size 2,443 bytes, and“761_190_030_US_Sequence_Listing_ST25.txt”, created on 2020 Feb. 14,modified on 2020 Feb. 14, file size 688 bytes, containing SEQ ID NO: 1,are incorporated by reference in their entirety herein.

FIELD OF THE INVENTION

Isotopically-stabilized tetronimide compounds comprising one or moredeuterium atoms, derivatives, and intermediates, thereof, includingmethods for their synthesis, pharmaceutical compositions thereof, andmethods of using these compounds to interact with target molecules incell-free samples, cell- and tissue-based assays, animal models, and ina subject are disclosed. One aspect relates to molecules that modulatethe expression or catalytic activity of aspartyl (asparaginyl)β-hydroxylase (ASPH) within or on the surface of a cell. Other aspectsof the invention relate to use of the molecules disclosed herein todiagnose, ameliorate, or treat cell proliferation disorders and relateddiseases. Related aspects include uses of the compounds to modulate theactivity of viruses, as anti-hyperlipidemia agents, and as agents toameliorate or treat thrombosis and related cardiovascular and metabolicdisorders.

BACKGROUND OF THE INVENTION

Aspartyl(asparaginyl)-β-hydroxylase (ASPH) is an iron-dependentdioxygenase that catalyzes the hydroxylation of β carbons of asparticacid and asparagine residues in calcium binding Epidermal Growth Factor(cbEG F)-like domains of a variety of proteins, including Notch andNotch ligand homologs (Dinchuk, Focht et al. 2002) extracellular matrixproteins, and low density lipoprotein (LDL) receptors. ASPH was firstobserved to be involved in the hydroxylation of a specific aspartic acidresidue in the blood coagulation cascade proteins (Drakenberg, Femlundet al. 1983), where the hydroxylated residue is underlined in theconsensus sequence CX[D/N]X₄[Y/F]XC (SEQ ID NO: 1). The role of thehydroxylated residue is presently unknown, but the sole known crystalstructure with a beta-hydroxylated asparagine (Crystal structuredeposited as 5JZZ in 2016, but annotated by Pfeffer et al, as to bepublished).

ASPH is generally classified as a peptide-aspartate beta-dioxygenase (EC1.14.11.16), a member of the alpha-ketoglutarate-dependent hydroxylasessuperfamily, which catalyzes the following chemical reaction,facilitated by iron as a cofactor.peptide-L-aspartate+2-oxoglutarate+O₂⇄peptide-3-hydroxy-L-aspartate+succinate+CO₂  (Reaction1)

ASPH is not normally expressed in adult cells (Lavaissiere, Jia et al.1996), but is expressed during invasion of the uterine wall bytrophoblasts during development of the placenta (Gundogan, Elwood et al.2007). ASPH is overexpressed in a variety of tumors, includinghepatocellular, cholangiocarcinoma, gastric cancer, pancreatic cancer,non-small cell lung cancer, glioblastoma multiform, osteosarcoma,cervical cancer, ovarian cancer and breast cancer (Yang, Song et al.2010), and enhances signaling in the Notch pathway (Cantarini, de laMonte et al. 2006).

FIG. 1 sets forth an illustration showing the Activation of NotchSignaling Pathway by ASPH. FIG. 2 (Panels A-H, plus domain key) and FIG.3 (Panels A-G, plus domain key) both set forth illustrations showing theLocations of Epitopes of Interest on ASPH.

Known and computationally predicted ASPH substrates are illustrated inFIG. 4 and FIG. 5. Prediction of ASPH substrates is based upon theprotein possessing A) a cbEGF domain and B) the consensus sequenceCX[D/N]X₄[Y/F]XC (SEQ ID NO: 1). Of particular interest are nearly allof the Notch signaling proteins, not only including the receptorsNotch1-4, but many of the known ligands such as Jagged1&2 and DII1&4,but also known Notch pathway modulator human homologues of Crumbs fromDrosophila. ASPH is known to hydroxylate lipid receptor proteins,including Lrp1. Lrp1 is known to have an interaction with Wnt5a of thecanonical Wnt signaling pathway (El Asmar, Terrand et al. 2016). ASPHsubstrate Gas6 is the ligand of the Tyro3, Axel and Mer (TAM) kinases,which have been implicated in cancer (Wu, Ma et al. 2018). Known ASPHsubstrates including the fibrillins are involved in the release ofTGF-beta, which is implicated in cancer (Furler, Nixon et al. 2018). Inaddition to cancer, ASPH hydroxylated substrates are found in nearly allof the blood coagulation proteins involved in thrombosis (see panel D inFIG. 2), and many of the proteins involved in lipid uptake includingLDLR, VLDLR and Lrp1 (see panel B in FIG. 2) and cholesterolhomeostasis. Thus, ASPH expression is expected to have a cascade ofeffects, but may have particular value in the treatment of cancer, aswell as thrombosis and lipid/cholesterol associated cardiovasculardiseases. ASPH expression may be correlated with viral infection,particularly with hepatitis B, D and human papillomavirus, and mayenhance viral replication either directly, by enhancing cellularproliferation, or by activating proteins (such as URG11/VWCE) that arespecifically upregulated by the virus.

ASPH is known to contain multiple phosphorylation sites (Tong, Gao etal. 2013), including T748. Phosphorylation of ASPH is known to alter theexpression and function of ASPH (Borgas, Gao et al. 2015), and plays apotential role in migration and tissue invasion of hepatocellularcarcinoma (Borgas, Gao et al. 2015). Antibodies selective for ASPHphosphorylation state should be useful in the diagnosis of cancer anddistinguishing ASPH expressed in normal cells compared to ASPH expressedin tumor cells.

Other strategies for modulating the expression or activity of ASPHinclude synthesis and testing of small molecule compounds that inhibitthe activity of the enzyme (Aihara, Huang et al. 2014), a cellularapproach relying on use of dendritic cells (Noda, Shimoda et al. 2012),and an approach directed to the synthesis and testing of vaccinesagainst ASPH and related polypeptides (Iwagami, Casulli et al. 2017).

U.S. Pat. No. 9,771,356 discloses ASPH modulating compounds that possessa stereocenter that is easily racemized, which cannot be isolated aspure enantiomers under experimental conditions. While deuteratedversions of existing drug products are known (Timmins, G. S., 2014), theuse of deuterium to limit racemization of the tetronimide ring core,permitting stable isolation of pure enantiomers as disclosed herein, issurprising and unexpected. The deuterated versions of many tetronimidecompounds disclosed herein have superior chemical and drug productproperties, compared to the properties of undeuterated tetronimidecompounds, precursor compounds, intermediates, and related derivatives.

SUMMARY OF THE INVENTION

Isotopically-stabilized tetronimide compounds comprising one or moredeuterium atoms, derivatives, and intermediates, thereof, includingmethods for their synthesis, pharmaceutical compositions thereof, andmethods of using these compounds to interact with target molecules incell-free samples, cell- and tissue-based assays, animal models, and inhuman and animal subjects are disclosed.

One aspect of the invention is directed to a deuterated compound of anyone of formulas {I-A, I-B, I-C, I-D, I-E, I-F, I-G, or I-H}:

or a salt, ester, metabolite, prodrug, or solvate thereof,

wherein Ar¹ is a substituted or unsubstituted C₆-C₂₀ aryl or 5- to20-membered heteroaryl;

wherein at least one of V¹, V², V³, V⁴, V⁵, or Z¹, Z², Z³, Z⁴, Z⁵, Z⁶,Z⁷, Z⁸, or Z⁹ is a deuterium atom (D) and any atom not designated asdeuterium is present as hydrogen (H, or not shown) at its naturalisotopic abundance;

wherein W is C(O), C(S), or S(O)₂;

wherein Y is a single bond, O, CR⁵⁰R⁵¹, or NR⁵² when W is CO and W is asingle bond, CR⁵⁰R⁵¹ or NR⁵² when X is SO₂, and

wherein R⁵³ is selected from the group consisting of substituted orunsubstituted C₁-C₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl,substituted or unsubstituted C₂-C₆ alkynyl, substituted or unsubstitutedC₆-C₂₀ aryl, substituted or unsubstituted C₇-C₂₆ arylalkyl, substitutedor unsubstituted 5 to 20-membered heteroaryl, and substituted orunsubstituted 6-26 membered heteroarylalkyl; and

wherein Ar², designated as an unsubstituted or substituted C₆-C₂₀heteroaryl is selected from the group consisting of: phenyl; naphthyl;pyridyl; pyridone; pyrimidine; pyradazine; pyrazine; purine; furan;thiophene; oxazole; thiazole; isoxazole; isothiazole; oxadiazole;thiadiazole; pyrrole; imidazole; triazole; tetrazole; and diazepine.

Also described are methods of synthesizing a deuterated compound of anyone of formulas {I-A, I-B, I-C, I-D, I-E, I-F, I-G, or I-H} from anunlabeled precursor compound and a donor molecule comprising one or moredeuterium atoms.

Also described are methods of using a deuterated compound of any one offormulas {I-A, I-B, I-C, I-D, I-E, I-F, I-G, or I-H} to facilitated themanufacture of a medicament, including pharmaceutically-acceptablecompositions comprising one or more excipients and the compound or asalt, ester, metabolite, prodrug, or solvate thereof.

Also described is use of a deuterated compound of any one of formulas{I-A, I-B, I-C, I-D, I-E, I-F, I-G, or I-H} to facilitate the diagnosis,treatment, or ameliorating of a condition associated with cellproliferation disorders and related diseases. Related aspects includeuses of the deuterated compounds to modulate the activity of viruses, oras anti-hyperlipidemia agents, and as agents to ameliorate or treatthrombosis and related cardiovascular and metabolic disorders.

BRIEF DESCRIPTION OF THE DRAWINGS

Statement Concerning Aspects of the Invention Understood by Reference tothe Drawings

The foregoing aspects and many of the attendant advantages of thisinvention will become more readily appreciated as the same become betterunderstood by reference to the following detailed description, whentaken in conjunction with the accompanying drawings, wherein:

FIG. 1 sets forth an illustration showing the Activation of NotchSignaling Pathway by ASPH.

FIG. 2 (Panels A-H, plus a polypeptide domain key) sets forth anillustration showing experimentally confirmed and computationallypredicted substrates of ASPH, including those found in the followingtypes of proteins: A. Notch signaling pathway, B. Lipid receptors, C.Blood coagulation cascade proteins, D. Thrombospondins, E. Complementcascade proteins, F. FAT cadherin domain proteins, G. Bone associatedproteins, and H. 7-transmembrane domain containing proteins.

FIG. 3 (Panels A-G, plus a polypeptide domain key) sets forth anillustration showing experimentally confirmed and computationallypredicted substrates of ASPH (continued), including those found in thefollowing types of proteins: A. TGF-b containing proteins, B. Plateletassociated proteins, C. Eye/retina associated proteins, D. Mammarycancer metastasis proteins, E. Slit proteins, F. Miscellaneous proteins,and G. Drosophila homologues.

FIG. 4 sets forth an illustration demonstrating the mechanism of actionof tetronimide modulating compounds. Deuterium can stabilize astereo-center, or can be used to slow down or suppress metabolism.Compound #2066 has a deuterium at the stereocenter, as well as twodeuteriums at the benzylic position adjacent to the “C” ring. Compound#2084 has two deuteriums on the amino of the tetronimide ring. Compound#2085 has a deuterium at the stereocenter, two deuteriums at thebenzylic position adjacent to the “C” ring, and two deuteriums on theamino of the tetronimide ring. Compound #1072 has two deuteriums at thebenzylic position adjacent to the “C” ring, and the “C” ring isperdeuterated. Compound #2087 is deuterated at the stereocenter, thebenzylic position adjacent to the “C” ring, two deuteriums on the amineof the tetronimide, and the “C” ring is perdeuterated. Compound #1084has the “A” ring perdeuterated.

FIG. 5 illustrates the synthesis of non-deuterated ASPH tetronimidemodulator compounds in Scheme 1. Scheme 2 illustrates the synthesis ofcompounds of the formulas {I-A} and {I-B}. Scheme 3 illustrates thesynthesis of compounds of the formula {I-D}. Scheme 4 illustrates thesynthesis of compounds of the formula {I-E}.

FIG. 6 illustrates an alternate synthesis of compounds of the formula{I-D}. Scheme 6 illustrates the synthesis of perdeuteratedphenylmethanesulfonyl chloride. Scheme 7 illustrates the synthesis ofcompounds of the formula {I-F}.

FIG. 7 illustrates the synthesis of compounds of the formula {I-G}according to Scheme 8. Scheme 9 illustrates the synthesis of compoundsof the formula {I-G}. Scheme 10 illustrates the synthesis of compoundsof the formula {I-H}.

FIG. 8 illustrates the Activities of Undeuterated, Racemic, andDeuterated Enantiomers of Tetronimide Modulator Compounds Against ASPHin Liver Microsome Assays.

FIG. 9 illustrates the Activities of Specific Compounds Against MCF-7Cells In Vitro.

FIGS. 10-1 to 10-62 illustrate the raw and tabulated NMR spectra of 21compounds over 62 pages for the compounds listed in Table 3, entitled“Table of Compounds by Informal Number and Chemical Name with NMRSpectra”.

TERMS AND DEFINITIONS

The following is a list of abbreviations, plus terms and theirdefinitions, used throughout the specification and the claims:

General abbreviations and their corresponding meanings include: aa orAA=amino acid; mg=milligram(s); ml or mL=milliliter(s);mm=millimeter(s); mM=millimolar; nmol=nanomole(s); pmol=picomole(s);ppm=parts per million; RT=room temperature; U=units; ug, μg=microgram(s); ul, μl=micro liter(s); uM, μM=micromolar, TEA=triethylamine,LDA=lithium diisopropyl amine, THF=tetrahydrofuran,DMAP=4-dimethylaminopyridine, DMF=N,N′-dimethylformamide.

Specific abbreviations and their corresponding meanings include:

The terms “cell” and “cells”, which are meant to be inclusive, refer toone or more cells which can be in an isolated or cultured state, as in acell line comprising a homogeneous or heterogeneous population of cells,or in a tissue sample, or as part of an organism, such as a transgenicanimal.

The term “modulator”, which is meant to be inclusive, refers to one ormore activities, such as stimulation of activity, inhibition ofenzymatic activity, stimulation of protein expression, or suppression ofprotein expression. Common examples of stimulation of activity includeallosteric activators. Common examples of inhibition of enzymaticactivity include allosteric deactivators, competitive inhibitors,non-competitive inhibitors, and uncompetitive inhibitors. Commonexamples of stimulation of protein expression include kinase inhibitorsor activators. Common examples of suppression of protein expressioninclude kinase inhibitors or activators.

The term “amino acid” encompasses both naturally occurring andnon-naturally occurring amino acids unless otherwise designated.

The phrase “isotopic enrichment factor” means the ratio between theisotopic abundance and the natural abundance of a specified isotope.

The term “isotopologue” means a species in which the chemical structurediffers from a specific compound of the invention only in the isotopiccomposition thereof.

The symbols “D” and “d” mean deuterium.

The terms “cell” and “cells”, which are meant to be inclusive, refer toone or more cells which can be in an isolated or cultured state, as in acell line comprising a homogeneous or heterogeneous population of cells,or in a tissue sample, or as part of an organism, such as an unmodifiedor a transgenic animal.

The term “an effective amount” means an amount of the substance inquestion which produces a statistically significant effect. For example,an “effective amount” for therapeutic uses is the amount of thecomposition comprising an active compound herein required to provide aclinically significant alteration in a measurable trait. Such effectiveamounts will be determined using routine optimization techniques and aredependent on the particular condition to be treated, the condition ofthe patient, the route of administration, dosage required for thecompounds of the invention is manifested as that which induces astatistically significant difference between treatment and controlgroups.

A “therapeutically effective amount” refers to an amount effective, atdosages and for periods of time necessary, to achieve the desiredtherapeutic result. A therapeutically effective amount of modulator mayvary according to factors such as the disease state, age, sex, andweight of the individual, and the ability of the modulator to elicit adesired response in the individual. Dosage regimens may be adjusted toprovide the optimum therapeutic response. A therapeutically-effectiveamount is also one in which any toxic or detrimental effects of themodulator are outweighed by the therapeutically beneficial effects.

A “prophylactically effective amount” refers to an amount effective, atdosages and for periods of time necessary, to achieve the desiredprophylactic result. A prophylactically effective amount can bedetermined as described above for the therapeutically-effective amount.Typically, since a prophylactic dose is used in subjects prior to or atan earlier stage of disease, the prophylactically effective amount willbe less than the therapeutically-effective amount.

As used herein, the term “cell proliferative disorder” refers toconditions in which unregulated or abnormal growth, or both, of cellscan lead to the development of an unwanted condition or disease, whichmay or may not be cancerous. Exemplary cell proliferative disorders thatmay be treated with the compounds of the invention encompass a varietyof conditions wherein cell division is deregulated. Exemplary cellproliferative disorder include, but are not limited to, neoplasms,benign tumors, malignant tumors, pre-cancerous conditions, in situtumors, encapsulated tumors, metastatic tumors, liquid tumors, solidtumors, immunological tumors, hematological tumors, cancers, carcinomas,leukemias, lymphomas, sarcomas, and rapidly dividing cells. The term“rapidly dividing cell” as used herein is defined as any cell thatdivides at a rate that exceeds or is greater than what is expected orobserved among neighboring or juxtaposed cells within the same tissue. Acell proliferative disorder includes a precancer or a precancerouscondition. A cell proliferative disorder includes cancer. The methodsand uses provided herein can be or may be used to treat or alleviate asymptom of cancer or to identify suitable candidates for such purposes.The term “cancer” includes solid tumors, as well as, hematologic tumorsand/or malignancies. A “precancer cell” or “precancerous cell” is a cellmanifesting a cell proliferative disorder that is a precancer or aprecancerous condition. A “cancer cell” or “cancerous cell” is a cellmanifesting a cell proliferative disorder that is a cancer. Anyreproducible means of measurement may be used to identify cancer cellsor precancerous cells. Cancer cells or precancerous cells can beidentified by histological typing or grading of a tissue sample (e.g., abiopsy sample). Cancer cells or precancerous cells can be identifiedthrough the use of appropriate molecular markers.

As used herein, “treating” or “treat” describes the management and careof a patient for the purpose of combating a disease, condition, ordisorder and includes the administration of a compound of the presentinvention, or a pharmaceutically acceptable salt, prodrug, metabolite,polymorph or solvate thereof, to alleviate the symptoms or complicationsof a disease, condition or disorder, or to eliminate the disease,condition or disorder. The term “treat” can also include treatment of acell in vitro or an animal model.

A compound of the present invention, or a pharmaceutically acceptablesalt, prodrug, metabolite, polymorph or solvate thereof, can or may alsobe used to prevent a relevant disease, condition or disorder, or used toidentify suitable candidates for such purposes. As used herein,“preventing,” “prevent,” or “protecting against” describes reducing oreliminating the onset of the symptoms or complications of such disease,condition or disorder.

As used herein, the term “alleviate” is meant to describe a process bywhich the severity of a sign or symptom of a disorder is decreased.Importantly, a sign or symptom can be alleviated without beingeliminated. The administration of pharmaceutical compositions of theinvention can or may lead to the elimination of a sign or symptom,however, elimination is not required. Effective dosages should beexpected to decrease the severity of a sign or symptom. For instance, asign or symptom of a disorder such as cancer, which can occur inmultiple locations, is alleviated if the severity of the cancer isdecreased within at least one of multiple locations.

As used herein, a “subject” is interchangeable with a “subject in needthereof”, both of which refer to a subject having a cell proliferationdisorder, or a subject having an increased risk of developing suchdisorder relative to the population at large. A “subject” includes amammal. The mammal can be e.g., a human or appropriate non-human mammal,such as primate, mouse, rat, dog, cat, cow, horse, goat, camel, sheep ora pig. The subject can also be a bird or fowl. In one aspect, the mammalis a human. A subject in need thereof can be one who has been previouslydiagnosed or identified as having cancer or a precancerous condition. Asubject in need thereof can also be one who has (e.g., is sufferingfrom) cancer or a precancerous condition. Alternatively, a subject inneed thereof can be one who has an increased risk of developing suchdisorder relative to the population at large (i.e., a subject who ispredisposed to developing such disorder relative to the population atlarge). A subject in need thereof can have a precancerous condition. Theterm “animal” includes human beings.

The term “optionally substituted” moiety refers to either unsubstitutedchemical moiety (e.g., alkyl, aryl, heteroaryl, etc.) or a chemicalmoiety having designated substituents replacing one or more hydrogenatoms on one or more carbons of the hydrocarbon backbone. Suchsubstituents can include, for example, alkyl, alkenyl, alkynyl, halogen,hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy,aryloxycarbonyloxy, carboxylate, alkylcarbonyl, arylcarbonyl,alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl,alkylthiocarbonyl, alkoxyl, phosphate, phosphonato, phosphinato, amino(including alkylamino, dialkylamino, arylamino, diarylamino andalkylarylamino), acylamino (including alkylcarbonylamino,arykarbonylamino, carbamoyl and ureido), amidino, imino, sulfhydryl,alkylthio, arylthio, thiocarboxylate, sulfates, alkylsulfinyl,sulfonato, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, azido,heterocyclyl, alkylaryl, or an aromatic or heteroaromatic moiety.

The term “substituted aryl or heteroaryl” refers to aromatic orheteroaromatic rings may contain one or more substituents such as —OH,SH, —CN, —F, —Cl, —Br, —R, —NO₂—NO, —NH2, —NHR, —NRR, —C(O)R, —C(O)OH,—C(O)OR, —C(O)NH2, —C(O)NHR, —C(O)NRR, and the like where each R isindependently (C₁-C₅) alkyl, substituted (C₁-C₆) alkyl, (C₂-C₆) alkenyl,substituted (C₂-C₆) alkenyl, (C₂-C₆) alkynyl, substituted (C₂-C₆)alkynyl, (C₅-C₂₀) aryl, substituted (C₅-C₂₀) aryl, (C₆-C₂₆) arylalkyl,substituted (C₆-C₂₆) arylalkyl, 5-20 membered heteroaryl, substituted5-20 membered heteroaryl, 6-26 membered heteroarylalkyl or substituted6-26 membered heteroarylalkyl.

An “arylalkyl” or an “aralkyl” moiety is an alkyl substituted with anaryl (e.g., phenylmethyl (benzyl)). An “alkylaryl” moiety is an arylsubstituted with an alkyl (e.g., methylphenyl).

A “derivative” of a compound X (e.g., a peptide or amino acid) refers toa form of X in which one or more reactive groups on the compound havebeen derivatized with a substituent group. Peptide derivatives includepep tides in which an amino acid side chain, the peptide backbone, orthe amino’ or carboxy-terminus has been derivatized (e.g., peptidiccompounds with 5 methylated amide linkages).

An “analogue” of a compound X refers to a compound which retainschemical structures of X necessary for functional activity of X yetwhich also contains certain chemical structures which differ from X. Ananalogue of a naturally-occurring peptide, is a peptide which includesone or more non-naturally-occurring amino acids.

The term “mimetic refers to a compound having similar functional and/orstructural properties to another known compound or a particular fragmentof that known compound. A “mimetic” of a compound X refers to a compoundin which chemical structures of X necessary for functional activity of Xhave been replaced with other chemical structures which mimic theconformation of X. The term mimetic, and in particular, peptidomimetic,is intended to include isosteres.

The term “cyclic group”, as used herein, is intended to include cyclicsaturated or unsaturated (i.e., aromatic) group having from about 3 to10, preferably about 4 to 8, and more preferably about 5 to 7, carbonatoms. Exemplary cyclic groups include cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, and cyclooctyl. Cyclic groups may beunsubstituted or substituted at one 35 or more ring positions. Thus, acyclic group may be substituted with halogens, alkyls, cycloalkyls,alkenyls, alkynyls, aryls, heterocycles, hydroxyls, aminos, nitros,thiols, amines, imines, amides, phosphonates, phosphines, carbonyls,carboxyls, silyls, ethers, thioethers, sulfonyls, sulfonates,selenoethers, ketones, aldehydes, esters, CF₃, CN, or the like.

The term “heterocyclic group” is intended to include cyclic saturated orunsaturated (i.e., aromatic) group having from about 3 to 10, preferablyabout 4 to 8, and more preferably about 5 to 7, carbon atoms, whereinthe ring structure includes about one to four heteroatoms. Heterocyclicgroups include pyrrolidine, oxolane, thiolane, imidazole, oxazole,piperidine, piperazine, morpholine and pyridine. The heterocyclic ringcan be substituted at one or more positions with such substituents as,for example, halogens, alkyls, cycloalkyls, alkenyls, alkynyls, aryls,other heterocycles, hydroxyl, amino, nitro, thiol, amines, imines,amides, phosphonates, phosphines, carbonyls, carboxyls, eilyls, ethers,thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, CF₃,CN, or the like. Heterocycles may also be bridged or fused to othercyclic groups as described below.

“Aryl” includes groups with aromaticity, including “conjugated,” ormulticyclic systems with at least one aromatic ring and do not containany heteroatom in the ring structure. Examples include phenyl, benzyl,1,2,3,4-tetrahydronaphthalenyl, etc.

“Heteroaryl” groups are aryl groups, as defined above, except havingfrom one to four heteroatoms in the ring structure, and may also bereferred to as “aryl heterocycles” or “heteroaromatics.” As used herein,the term “heteroaryl” is intended to include a stable 5-, 6-, or7-membered monocyclic or 7-, 8-, 9-, 10-, 11- or 12-membered bicyclicaromatic heterocyclic ring which consists of carbon atoms and one ormore heteroatoms, e.g., 1 or 1-2 or 1-3 or 1-4 or 1-5 or 1-6heteroatoms, or e.g., 1, 2, 3, 4, 5, or 6 heteroatoms, independentlyselected from the group consisting of nitrogen, oxygen and sulfur. Thenitrogen atom may be substituted or unsubstituted (i.e., N or NR whereinR is H or other substituents, as defined). The nitrogen and sulfurheteroatoms may optionally be oxidized (i.e., N→O and S(O)_(p), wherep=1 or 2). It is to be noted that total number of S and O atoms in thearomatic heterocycle is not more than 1.

Examples of heteroaryl groups include pyrrole, furan, thiophene,thiazole, isothiazole, imidazole, triazole, tetrazole, pyrazole,oxazole, isoxazole, pyridine, pyrazine, pyridazine, pyrimidine, and thelike.

Furthermore, the terms “aryl” and “heteroaryl” include multiyclic aryland heteroaryl groups, e.g., tricyclic, bicyclic, e.g., naphthalene,benzoxazole, benzodioxazole, benzothiazole, benzoimidazole,benzothiophene, methylenedioxyphenyl, quinoline, isoquinoline,naphthrydine, indole, benzofuran, purine, benzofuran, deazapurine,indolizine.

In the case of multicyclic aromatic rings, only one of the rings needsto be aromatic (e.g., 2,3-dihydroindole), although all of the rings maybe aromatic (e.g., quinoline). The second ring can also be fused orbridged.

The cycloalkyl, heterocycloalkyl, aryl, or heteroaryl ring can besubstituted at one or more ring positions (e.g., the ring-forming carbonor heteroatom such as N) with such substituents as described above, forexample, alkyl, alkenyl, alkynyl, halogen, hydroxyl, alkoxy,alkykarbonyloxy, arykarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy,carboxylate, alkykarbonyl, alkylaminocarbonyl, aralkylaminocarbonyl,alkenylaminocarbonyl, alkylcarbonyl, arykarbonyl, aralkylcarbonyl,alkenylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylthiocarbonyl,phosphate, phosphonato, phosphinato, amino (including alkylamino,dialkylamino, arylamino, diarylamino and alkylarylamino), acylamino(including alkykarbonylamino, arylcarbonylamino, carbamoyl and ureido),amidino, imino, sulfhydryl, alkylthio, arythio, thiocarboxylate,sulfates, alkylsulfinyl, sulfonato, sulfamoyl, sulfonamido, nitro,trifluoromethyl, cyano, azido, heterocyclyl, alkylaryl, or an aromaticor heteroaromatic moiety. Aryl and heteroaryl groups can also be fusedor bridged with alicyclic or heterocyclic rings, which are not aromaticso as to form a multiyclic system (e.g., tetralin,methylenedioxyphenyl).

The term “polycyclic group” as used herein is intended to refer to twoor more saturated or unsaturated (i.e., aromatic) cyclic rings in whichtwo or more carbons are common to two adjoining rings, e.g., the ringsare “fused rings”. Rings that are joined through non-adjacent atoms aretermed “bridged” rings. Each of the rings of the polycyclic group can besubstituted with such substituents as described above, as for example,halogens, alkyls, cycloalkyls, alkenyls, alkynyls, hydroxyl, amino,nitro, thiol, amines, imines, amides, phosphonates, phosphines,carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls,selenoethers, ketones, aldehydes, esters, CF₃, CN, or the like.

As used herein, the term “modulating group” and “modifying group” areused interchangeably to describe a chemical group directly or indirectlyattached, generally, to a peptidic structure. For example, a modifyinggroup(s) can be directly attached by covalent coupling to a peptidicstructure or a modifying group(s) can be attached indirectly by a stablenon-covalent association.

The compounds described herein include the compounds themselves, as wellas their salts, their solvates, and their prodrugs, if applicable. Asalt, for example, can be formed between an anion and a positivelycharged group (e.g., amino) on a substituted benzene compound. Suitableanions include chloride, bromide, iodide, sulfate, bisulfate, sulfamate,nitrate, phosphate, citrate, methanesulfonate, trifluoroacetate,glutamate, glucuronate, glutarate, malate, maleate, succinate, fumarate,tartrate, tosylate, salicylate, lactate, naphthalenesulfonate, andacetate (e.g., trifluoroacetate). The term “pharmaceutically acceptableanion” refers to an anion suitable for forming a pharmaceuticallyacceptable salt. Likewise, a salt can also be formed between a cationand a negatively charged group (e.g., carboxylate) on a substitutedbenzene compound. Suitable cations include sodium ion, potassium ion,magnesium ion, calcium ion, and an ammonium cation such astetramethylammonium ion. The substituted benzene compounds also includethose salts containing quaternary nitrogen atoms.

Examples of prodrugs include esters and other pharmaceuticallyacceptable derivatives, which, upon administration to a subject, arecapable of providing active substituted benzene compounds.

The compounds of the present invention, for example, the salts of thecompounds, can also exist in either hydrated or unhydrated (theanhydrous) form or as solvates with other solvent molecules. Nonlimitingexamples of hydrates include monohydrates, dihydrates, etc. Nonlimitingexamples of solvates include ethanol solvates, acetone solvates, etc.

“Solvate” means solvent addition forms that contain eitherstoichiometric or non-stoichiometric amounts of solvent. Some compoundshave a tendency to trap a fixed molar ratio of solvent molecules in thecrystalline solid state, thus forming a solvate. If the solvent is waterthe solvate formed is a hydrate; and if the solvent is alcohol, thesolvate formed is an alcoholate. Hydrates are formed by the combinationof one or more molecules of water with one molecule of the substance inwhich the water retains its molecular state as H₂O.

The structural formula of the compound generally represents a certainisomer for convenience in some cases, but the present invention includesall isomers, such as geometrical isomers, optical isomers based on anasymmetrical carbon, stereoisomers, tautomers, and the like, it beingunderstood that not all isomers may have the same level of activity. Inaddition, a crystal polymorphism may be present for the compoundsrepresented by the formula. It is noted that any crystal form, crystalform mixture, or anhydride or hydrate thereof is included in the scopeof the present invention. Furthermore, so-called metabolite which isproduced by degradation of the present compound in vivo is included inthe scope of the present invention.

“Tautomer” is one of two or more structural isomers that exist inequilibrium and is readily converted from one isomeric form to another.This conversion results in the formal migration of a hydrogen atomaccompanied by a switch of adjacent conjugated double bonds. Tautomersexist as a mixture of a tautomeric set in solution. In solutions wheretautomerization is possible, a chemical equilibrium of the tautomerswill be reached. The exact ratio of the tautomers depends on severalfactors, including temperature, solvent and pH. The concept of tautomersthat are interconvertable by tautomerizations is called tautomerism.

Of the various types of tautomerism that are possible, two are commonlyobserved. In keto-enol tautomerism a simultaneous shift of electrons anda hydrogen atom occurs. Ring-chain tautomerism arises as a result of thealdehyde group (—CHO) in a sugar chain molecule reacting with one of thehydroxy groups (—OH) in the same molecule to give it a cyclic(ring-shaped) form as exhibited by glucose.

Common tautomeric pairs are: ketone-enol, amide-nitrile, lactam-lactim,amide-imidic acid tautomerism in heterocyclic rings (e.g., innucleobases such as guanine, thymine and cytosine), imine-enamine andenamine-enamine. An example of ketone-enol tautomerism in thetetronimide ring system is illustrated below.

A small molecule is a compound that is less than 2000 Daltons in mass.The molecular mass of the small molecule is preferably less than 1000Daltons, more preferably less than 600 Daltons, e.g., the compound isless than 500 Daltons, 400 Daltons, 300 Daltons, 200 Daltons, or 100Daltons.

The transitional term “comprising,” which is synonymous with“including,” “containing,” or “characterized by,” is inclusive oropen-ended and does not exclude additional, unrecited elements or methodsteps. By contrast, the transitional phrase “consisting of” excludes anyelement, step, or ingredient not specified in the claim. Thetransitional phrase “consisting essentially of” limits the scope of aclaim to the specified materials or steps “and those that do notmaterially affect the basic and novel characteristic(s)” of the claimedinvention.

Compounds such as small molecule inhibitors, polynucleotides,polypeptides, or other agents are purified and/or isolated. Purifiedcompounds are at least 60% by weight (dry weight) the compound ofinterest. Preferably, the preparation is at least 75%, more preferablyat least 90%, and most preferably at least 99%, by weight the compoundof interest. For example, a purified compound is one that is at least90%, 91%, 92%, 93%, 94%, 95%, 98%, 99%, or 100% (w/w) of the desiredcompound by weight. Purity is measured by any appropriate standardmethod, for example, by column chromatography, thin layerchromatography, or high-performance liquid chromatography (HPLC)analysis. A purified or isolated polynucleotide (ribonucleic acid (RNA)or deoxyribonucleic acid (DNA)) is free of the genes or sequences thatflank it in its naturally-occurring state. An “isolated” or “purified”nucleic acid molecule, polynucleotide, polypeptide, or protein, issubstantially free of other cellular material, or culture medium whenproduced by recombinant techniques, or chemical precursors or otherchemicals when chemically synthesized. Purified also defines a degree ofsterility that is safe for administration to a human subject, e.g.,lacking infectious or toxic agents.

DETAILED DESCRIPTION

One aspect of the invention is directed to a deuterated compound of anyone of formulas {I-A, I-B, I-C, I-D, I-E, I-F, I-G, or I-H}:

or a salt, ester, metabolite, prodrug, or solvate thereof,

wherein Ar¹ is a substituted or unsubstituted C₆-C₂₀ aryl or 5-to20-membered heteroaryl;

wherein at least one of V¹, V², V³, V⁴, V⁵, or Z¹, Z², Z³, Z⁴, Z⁵, Z⁶,Z⁷, Z⁸, or Z⁹ is a deuterium atom (D) and any atom not designated asdeuterium is present as hydrogen (H, or not shown) at its naturalisotopic abundance;

wherein W is C(O), C(S), or S(O)₂;

wherein Y is a single bond, O, CR⁵⁰R⁵¹, or NR⁵² when W is CO and W is asingle bond, CR⁵⁰R⁵¹ or NR⁵² when X is SO₂, and

wherein R⁵³ is selected from the group consisting of substituted orunsubstituted C₁-C₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl,substituted or unsubstituted C₂-C₆ alkynyl, substituted or unsubstitutedC₆-C₂₀ aryl, substituted or unsubstituted C₇-C₂₆ arylalkyl, substitutedor unsubstituted 5 to 20-membered heteroaryl, and substituted orunsubstituted 6-26 membered heteroarylalkyl; and

wherein Ar², designated as an unsubstituted or substituted C₆-C₂₀heteroaryl is selected from the group consisting of: phenyl; naphthyl;pyridyl; pyridone; pyrimidine; pyradazine; pyrazine; purine; furan;thiophene; oxazole; thiazole; isoxazole; isothiazole; oxadiazole;thiadiazole; pyrrole; imidazole; triazole; tetrazole; and diazepine.

Another aspect is directed to a deuterated compound having formula{I-A},

or a salt, ester, metabolite, prodrug, or solvate thereof, wherein V¹ isdeuterium (D) and any atom not designated as deuterium is present ashydrogen (H, or not shown) at its natural isotopic abundance.

Another aspect is directed to a deuterated compound having formula{I-B},

or a salt, ester, metabolite, prodrug, or solvate thereof, wherein atleast one of V¹, V², and V³ is a deuterium atom (D) and any atom notdesignated as deuterium is present as hydrogen (H, or not shown) at itsnatural isotopic abundance;

Another aspect is directed to a deuterated compound having formula{I-C},

or a salt, ester, metabolite, prodrug, or solvate thereof, wherein atleast one of V¹, V², V³, or Z¹, Z², Z³, Z⁴, and Z⁵ is a deuterium atom(D) and any atom not designated as deuterium is present as hydrogen (H,or not shown) at its natural isotopic abundance.

Another aspect is directed to a deuterated compound having formula{I-D},

or a salt, ester, metabolite, prodrug, or solvate thereof, wherein atleast one of V⁴ or V⁵ is a deuterium atom (D) and any atom notdesignated as deuterium is present as hydrogen (H, or not shown) at itsnatural isotopic abundance.

Another aspect is directed to a deuterated compound having formula{I-E},

or a salt, ester, metabolite, prodrug, or solvate thereof, wherein atleast one of V¹, V², V³, V⁴, or V⁵ is a deuterium atom (D) and any atomnot designated as deuterium is present as hydrogen (H, or not shown) atits natural isotopic abundance.

Another aspect is directed to a deuterated compound having formula{I-F},

or a salt, ester, metabolite, prodrug, or solvate thereof, wherein atleast one of V², V³, or Z¹, Z², Z³, Z⁴, or Z⁵ is a deuterium atom (D)and any atom not designated as deuterium is present as hydrogen (H, ornot shown) at its natural isotopic abundance.

Another aspect is directed to a deuterated compound having formula{I-G},

or a salt, ester, metabolite, prodrug, or solvate thereof, wherein atleast one of V¹, V², V³, V⁴, V⁵, or Z¹, Z², Z³, Z⁴, Z⁵ is a deuteriumatom (D) and any atom not designated as deuterium is present as hydrogen(H, or not shown) at its natural isotopic abundance.

Another aspect is directed to a deuterated compound having formula{I-H},

or a salt, ester, metabolite, prodrug or solvate thereof, wherein atleast one of V², V³, Z¹, Z², Z³, Z⁴, Z⁵, Z⁶, Z⁷, Z⁸, or Z⁹ is adeuterium atom (D) and any atom not designated as deuterium is presentas hydrogen (H, or not shown) at its natural isotopic abundance.

Another aspect relates to a deuterated compound having any one offormulas {I-A, I-B, I-C, I-D, I-E, I-F, or I-G} wherein Ar¹ is asubstituted C₆-C₂₀ aryl group selected from the group consisting of oneor more substituents selected from the group consisting of mono F, Cl,or Br at any position; difluoro or dichloro at different positions; monoand di methyl any position; mono di and trifluoromethyl; mono and di OMeat any position; mono and di chlorophenyl at any position; CO₂Me; F andCO₂Me; CO₂Et; C(O)CH3; C(O)NH₂; C(O):ND₂; COO⁻Na⁺; [COO⁻]₂Mg⁺²;[COO⁻]₂Ca⁺²; mono and di CN at different positions; phenyl; CF₃; CO₃Me;CO₂Et; CO₂D; CO₂Me and F; CF₃; CO₂Me; CO₂Et; CO₂D; CO₂Me;benzo[d][1,3]dixol-5-yl; and difluorobenzo[d][1,3]dixol-5-yl.

Another aspect relates to a deuterated compound having formula {I-A},wherein R⁵³ is Ar², designated as an unsubstituted or substituted C₆-C₂₀heteroaryl selected from the group consisting of: phenyl; naphthyl;pyridyl; pyridone; pyrimidine; pyradazine; pyrazine; purine; furan;thiophene; oxazole; thiazole; isoxazole; isothiazole; oxadiazole;thiadiazole; pyrrole; imidazole; triazole; tetrazole; and diazepine.

Another aspect relates to a deuterated compound having formula {I-A},wherein R⁵³ is a unsubstituted or substituted phenyl, selected from thegroup consisting of one or more substituents selected from the groupconsisting of: mono F, Cl, or Br at any position; difluoro or dichloroat different positions; mono and di methyl any position; mono di andtrifluoromethyl; mono and di OMe at any position; mono and dichlorophenyl at any position; CO₂Me; F and CO₂Me; CO₂Et; C(O)CH₃;C(O)NH₂; C(O):ND₂; COO⁻Na⁺; COO⁻K⁺; [COO⁻]₂Mg⁺²; [COO⁻]₂Ca⁺²; mono anddi CN at different positions; phenyl; CF₃; CO₃Me; CO₂D; CF₃; CO₂Me;benzo[d][1,3]dixol-5-yl; and difluorobenzo[d][1,3]dixol-5-yl.

Another aspect relates to a deuterated compound wherein any atom notdesignated as deuterium is present at its natural isotopic abundance,and where the percentage of isotopic enrichment for each designateddeuterium is at least 50%. Related aspects also include compounds wherethe enrichment for each designated deuterium is at least 75%, 90%, 95%,and 99%.

Another aspect of the invention relates to a method of preparing adeuterated compound having any of formulas {I-A, I-B, I-C, I-F} bycontacting an undeuterated precursor compound with a suitable base and adeuterated solvent. In one aspect, said suitable base is selected fromthe group consisting of LiOD, NaOD, KOD, CsOD, Ba(OD)₂, Ca(OD)₂,Mg(OD)₂, Mn(OD)₂, Li₂CO₃, Na₂CO₃, K₂CO₃, Cs₂CO₃, MgCO₃, and CaCO₃. Inanother aspect, said deuterated solvent is D₂O.

Another aspect relates to a method of preparing a deuterated compoundhaving formula {I-D}, by contacting an undeuterated precursor compoundwith deuterium in an acidic medium. In one aspect, said deuterium in anacidic medium is selected from the group consisting of one or more ofD₂O, DF, DCI, DBr, DI, D₂NO₃, D₂SO₄, CF₃SO₃D, CD₃CO₂D, CF₃CO₂D,CCl₃CO₂D.

Another aspect relates to a method of preparing a deuterated compoundhaving any one of formulas {I-E, I-G}, by contacting an undeuteratedprecursor compound with an acidic medium followed by a deuterated baskmedium. In one aspect, said acidic medium is selected from the groupconsisting of one or more of D₂O, DF, DCl, DBr, DI, D₂NO₃, D₂SO₄,CF₃SO₃D, CD₃CO₂D, CF₃CO₂D, CCl₃CO₂D. In another aspect said deuteratedbasic medium is selected from the group consisting of LiOD, NaOD, KOD,CsOD, Ba(OD)₂, Ca(OD)₂, Mg(OD)₂, Mn(OD)₂, Li₂CO₃, Na₂CO₃, K₂CO₃, Cs₂CO₃,MgCO₃, and CaCO₃.

Another aspect relates to a method of preparing a deuterated compound ofClaim 1 having any one of formulas {I-F, I-H}, by contacting anundeuterated precursor tetronimide compound with a deuterated sulfonylchloride. In one aspect, said deuterated sulfonyl chloride is selectedfrom the group consisting of d5-sulfonyl chloride and d7-sulfonylchloride.

Specific aspects of the invention include a deuterated compound selectedfrom the group consisting of racemic and (R) and (S) forms of a compoundselected from the group consisting of:

2001 2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dmethanesulfonate-d3; 2001(R)(R)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dmethanesulfonate-d3; 2001(S)(S)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dmethanesulfonate-d3; 20022-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dethane-1-sulfonate-1,1-d2; 2002(R)(R)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dethane-1-sulfonate-1,1-d2; 2002(S)(S)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dethane-1-sulfonate-1,1-d2; 20032-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dpropane-1-sulfonate-1,1-d2; 2003(R)(R)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dpropane-1-sulfonate-1,1-d2; 2003(S)(S)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dpropane-1-sulfonate-1,1-d2; 20042-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dpropane-2-sulfonate-2-d; 2004(R)(R)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dpropane-2-sulfonate-2-d; 2004(S)(S)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dpropane-2-sulfonate-2-d; 20052-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dbutane-1-sulfonate-1,1-d2; 2005(R)(R)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dbutane-1-sulfonate-1,1-d2; 2005(S)(S)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dbutane-1-sulfonate-1,1-d2; 20062-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d2-methylpropane-1-sulfonate-1,1-d2; 2006(R)(R)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d2-methylpropane-1-sulfonate-1,1-d2; 2006(S)(S)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d2-methylpropane-1-sulfonate-1,1-d2; 20072-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dbenzenesulfonate; 2007(R)(R)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dbenzenesulfonate; 2007(S)(S)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dbenzenesulfonate; 20082-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2008(R)(R)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2008(S)(S)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20092-amino-5-(2-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2009(R)(R)-2-amino-5-(2-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2009(S)(S)-2-amino-5-(2-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20102-amino-5-(3-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2010(R)(R)-2-amino-5-(3-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2010(S)(S)-2-amino-5-(3-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20112-amino-5-(2,3-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2011(R)(R)-2-amino-5-(2,3-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2011(S)(S)-2-amino-5-(2,3-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20122-amino-5-(2,4-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2012(R)(R)-2-amino-5-(2,4-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2012(S)(S)-2-amino-5-(2,4-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20132-amino-5-(2,5-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2013(R)(R)-2-amino-5-(2,5-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2013(S)(S)-2-amino-5-(2,5-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20142-amino-5-(3,4-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2014(R)(R)-2-amino-5-(3,4-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2014(S)(S)-2-amino-5-(3,4-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20152-amino-5-(3,5-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2015(R)(R)-2-amino-5-(3,5-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2015(S)(S)-2-amino-5-(3,5-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2016 methyl3-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2016(R) methyl(R)-3-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2016(S) methyl(S)-3-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2017 methyl4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonypoxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2017(R) methyl(R)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonypoxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2017(S) methyl(S)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonypoxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2018 methyl4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonypoxy)-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;2018(R) methyl(R)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonypoxy)-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;2018(S) methyl(S)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonypoxy)-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;2019 ethyl4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonypoxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2019(R) ethyl(R)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonypoxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2019(S) ethyl(S)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonypoxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2020 5-(4-acetylphenyl)-2-amino-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2020(R)(R)-5-(4-acetylphenyl)-2-amino-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2020(S)(S)-5-(4-acetylphenyl)-2-amino-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20212-amino-5-(4-carbamoylphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2021(R)(R)-2-amino-5-(4-carbamoylphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2021(S)(S)-2-amino-5-(4-carbamoylphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20224-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonypoxy)-2,3-dihydrofuran-2-yl-2-d)benzoicacid-d; 2022(R)(R)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonypoxy)-2,3-dihydrofuran-2-yl-2-d)benzoicacid-d; 2022(S)(S)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonypoxy)-2,3-dihydrofuran-2-yl-2-d)benzoicacid-d; 2023 sodium4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonypoxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2023(R) sodium(R)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonypoxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2023(S) sodium(S)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonypoxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2024 potassium4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonypoxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2024(R) potassium(R)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonypoxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2024(S) potassium(S)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonypoxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2027 2-amino-5-(2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2027(R)(R)-2-amino-5-(2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2027(S)(S)-2-amino-5-(2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20282-amino-5-(3-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2028(R)(R)-2-amino-5-(3-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2028(S)(S)-2-amino-5-(3-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20292-amino-5-(4-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2029(R)(R)-2-amino-5-(4-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2029(S)(S)-2-amino-5-(4-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20302-amino-5-(2,3-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2030(R)(R)-2-amino-5-(2,3-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2030(S)(S)-2-amino-5-(2,3-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20312-amino-5-(2,4-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2031(R)(R)-2-amino-5-(2,4-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2031(S)(S)-2-amino-5-(2,4-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20322-amino-5-(2,5-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2032(R)(R)-2-amino-5-(2,5-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2032(S)(S)-2-amino-5-(2,5-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20332-amino-5-(2,6-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2033(R)(R)-2-amino-5-(2,6-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2033(S)(S)-2-amino-5-(2,6-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20342-amino-5-(3,4-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2034(R)(R)-2-amino-5-(3,4-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2034(S)(S)-2-amino-5-(3,4-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20352-amino-5-(3,5-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2035(R)(R)-2-amino-5-(3,5-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2035(S)(S)-2-amino-5-(3,5-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20362-amino-5-(2-methoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2036(R)(R)-2-amino-5-(2-methoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2036(S)(S)-2-amino-5-(2-methoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20372-amino-5-(3-methoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2037(R)(R)-2-amino-5-(3-methoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2037(S)(S)-2-amino-5-(3-methoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20382-amino-5-(4-methoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2038(R)(R)-2-amino-5-(4-methoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2038(S)(S)-2-amino-5-(4-methoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20392-amino-5-(2,3-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2039(R)(R)-2-amino-5-(2,3-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2039(S)(S)-2-amino-5-(2,3-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20402-amino-5-(2,4-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2040(R)(R)-2-amino-5-(2,4-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2040(S)(S)-2-amino-5-(2,4-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20412-amino-5-(2,5-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2041(R)(R)-2-amino-5-(2,5-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2041(S)(S)-2-amino-5-(2,5-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20422-amino-5-(2,6-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2042(R)(R)-2-amino-5-(2,6-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2042(S)(S)-2-amino-5-(2,6-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20432-amino-5-(3,4-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2043(R)(R)-2-amino-5-(3,4-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2043(S)(S)-2-amino-5-(3,4-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20442-amino-5-(3,5-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2044(R)(R)-2-amino-5-(3,5-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2044(S)(S)-2-amino-5-(3,5-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20452-amino-5-(2-bromophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2045(R)(R)-2-amino-5-(2-bromophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2045(S)(S)-2-amino-5-(2-bromophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20462-amino-5-(3-bromophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2046(R)(R)-2-amino-5-(3-bromophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2046(S)(S)-2-amino-5-(3-bromophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20472-amino-5-(4-bromophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2047(R)(R)-2-amino-5-(4-bromophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2047(S)(S)-2-amino-5-(4-bromophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20482-amino-5-(2-chloro-3-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2048(R)(R)-2-amino-5-(2-chloro-3-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2048(S)(S)-2-amino-5-(2-chloro-3-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20492-amino-5-(2-chloro-4-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2049(R)(R)-2-amino-5-(2-chloro-4-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2049(S)(S)-2-amino-5-(2-chloro-4-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20502-amino-5-(2-chloro-5-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2050(R)(R)-2-amino-5-(2-chloro-5-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2050(S)(S)-2-amino-5-(2-chloro-5-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20512-amino-5-(2-chloro-6-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2051(R)(R)-2-amino-5-(2-chloro-6-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2051(S)(S)-2-amino-5-(2-chloro-6-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20522-amino-5-(3-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2052(R)(R)-2-amino-5-(3-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2052(S)(S)-2-amino-5-(3-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20532-amino-5-(3-chloro-4-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2053(R)(R)-2-amino-5-(3-chloro-4-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2053(S)(S)-2-amino-5-(3-chloro-4-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20542-amino-5-(3-chloro-5-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2054(R)(R)-2-amino-5-(3-chloro-5-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2054(S)(S)-2-amino-5-(3-chloro-5-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20552-amino-5-(5-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2055(R)(R)-2-amino-5-(5-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2055(S)(S)-2-amino-5-(5-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20562-amino-5-(4-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2056(R)(R)-2-amino-5-(4-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2056(S)(S)-2-amino-5-(4-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20572-amino-5-(4-chloro-3-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2057(R)(R)-2-amino-5-(4-chloro-3-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2057(S)(S)-2-amino-5-(4-chloro-3-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20582-amino-4-oxo-5-(o-tolyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2058(R)(R)-2-amino-4-oxo-5-(o-tolyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2058(S)(S)-2-amino-4-oxo-5-(o-tolyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20592-amino-4-oxo-5-(m-tolyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2059(R)(R)-2-amino-4-oxo-5-(m-tolyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2059(S)(S)-2-amino-4-oxo-5-(m-tolyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20602-amino-4-oxo-5-(p-tolyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2060(R)(R)-2-amino-4-oxo-5-(p-tolyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2060(S)(S)-2-amino-4-oxo-5-(p-tolyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20612-amino-5-(3-cyanophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2061(R)(R)-2-amino-5-(3-cyanophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2061(S)(S)-2-amino-5-(3-cyanophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20622-amino-5-(4-cyanophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2062(R)(R)-2-amino-5-(4-cyanophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2062(S)(S)-2-amino-5-(4-cyanophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20632-amino-4-oxo-5-phenyl-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2063(R)(R)-2-amino-4-oxo-5-phenyl-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2063(S)(S)-2-amino-4-oxo-5-phenyl-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20642-amino-4-oxo-5-(2-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2064(R)(R)-2-amino-4-oxo-5-(2-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2064(S)(S)-2-amino-4-oxo-5-(2-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20652-amino-4-oxo-5-(3-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2065(R)(R)-2-amino-4-oxo-5-(3-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2065(S)(S)-2-amino-4-oxo-5-(3-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20662-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2066(R)(R)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2066(S)(S)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20672-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d(4-fluorophenyl)methanesulfonate-d2; 2067(R)(R)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d(4-fluorophenyl)methanesulfonate-d2; 2067(S)(S)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d(4-fluorophenyl)methanesulfonate-d2; 2068 methyl4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)benzoate;2068(R) methyl(R)-4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)benzoate;2068(S) methyl(S)-4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)benzoate;2069 ethyl4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)benzoate;2069(R) ethyl(R)-4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)benzoate;2069(S) ethyl(S)-4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)benzoate;20704-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)benzoicacid-d; 2070(R)(R)-4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)benzoicacid-d; 2070(S)(S)-4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)benzoicacid-d; 2071 methyl4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;2071(R) methyl(R)-4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;2071(S) methyl(S)-4-(5-amino-4-((((4-fluorophenyOmethyl-d2)sulfonypoxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;20722-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d(phenyl-d5)methanesulfonate-d2; 2072(R)(R)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d(phenyl-d5)methanesulfonate-d2; 2072(S)(S)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d(phenyl-d5)methanesulfonate-d2; 2073 methyl4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2073(R) methyl(R)-4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2073(S) methyl(S)-4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2074 ethyl4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2074(R) ethyl(R)-4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2074(S) ethyl(S)-4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;20754-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoicacid-d; 2075(R)(R)-4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoicacid-d; 2075(S)(S)-4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoicacid-d; 2076 methyl4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;2076(R) methyl(R)-4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;2076(S) methyl(S)-4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;20772-amino-5-(benzo[d][1,3]dioxo1-5-yl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2077(R)(R)-2-amino-5-(benzo[d][1,3]dioxol-5-yl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2077(S)(S)-2-amino-5-(benzo[d][1,3]dioxol-5-yl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20782-amino-5-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2078(R)(R)-2-amino-5-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2078(S)(S)-2-amino-5-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2079 methyl2-(4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonypoxy)-2,3-dihydrofuran-2-yl-2-d)phenylacetate-d2;2079(R) methyl(R)-2-(4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonypoxy)-2,3-dihydrofuran-2-yl-2-d)phenylacetate-d2;2079(S) methyl(S)-2-(4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonypoxy)-2,3-dihydrofuran-2-yl-2-d)phenylacetate-d2;2080 2-amino-5-(4-(carbamoyl-d2)phenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2080(R)(R)-2-amino-5-(4-(carbamoyl-d2)phenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2080(S)(S)-2-amino-5-(4-(carbamoyl-d2)phenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20812-amino-4-oxo-5-(6-(trifluoromethyl)pyridin-3-yl-)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2081(R)(R)-2-amino-4-oxo-5-(6-(trifluoromethyppyridin-3-yl-)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2081(S)(S)-2-amino-4-oxo-5-(6-(trifluoromethyppyridin-3-yl-)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20822-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d(4-chlorophenyl)methanesulfonate-d2; 2082(R)(R)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d(4-chlorophenyl)methanesulfonate-d2; 2082(S)(S)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d(4-chlorophenyl)methanesulfonate-d2; 20832-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d(4-(trifluoromethyl)phenyl) methanesulfonate-d2; 2083(R)(R)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d(4-(trifluoromethyl)phenyl) methanesulfonate-d2; 20842-(amino-d2)-4-oxo-5-(4-(trifluoromethypphenyl)-4,5-dihydrofuran-3-ylphenylmethanesulfonate; 20852-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2085(R)(R)-2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2085(S)(S)-2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20862-(amino-d2)-4-oxo-5-(4-(trifluoromethypphenyl)-4,5-dihydrofuran-3-yl(phenyl-d5)methanesulfonate; 20872-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d(phenyl-d5) methanesulfonate-d2; 2087(R)(R)-2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d(phenyl-d5) methanesulfonate-d2; 2087(S)(S)-2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d(phenyl-d5) methanesulfonate-d2; 20882-(amino-d2)-4-oxo-5-(4-(trifluoromethypphenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-phenylmethanesulfonate; 20892-amino-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2089(R)(R)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2089(S)(S)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20902-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2090(R)(R)-2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2090(S)(S)-2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20912-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl(phenyl-d5) methanesulfonate; 20922-amino-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d(phenyl-d5) methanesulfonate-d2; 2092(R)(R)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d(phenyl-d5) methanesulfonate-d2; 2092(S)(S)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d(phenyl-d5) methanesulfonate-d2; 20932-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d(phenyl-d5) methanesulfonate-d2; 2093(R)(R)-2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d(phenyl-d5) methanesulfonate-d2; and 2093(S)(S)-2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d(phenyl-d5) methanesulfonate-d2.

Another specific aspect is a deuterated compound of having formula I-B.

Another specific aspect is a deuterated compound of having formula I-B,wherein Ar² is phenyl, and Ar¹ is a substituted C₆-C₂₀ aryl groupselected from the group consisting of one or more substituents selectedfrom the group consisting of mono F, Cl, or Br at any position; difluoroor dichloro at different positions; mono and di methyl any position;mono di and trifluoromethyl; mono and di OMe at any position; mono anddi chlorophenyl at any position; CO₂Me; F and CO₂Me; CO₂Et; C(O)CH₃;C(O)NH₂; C(O):ND₂; COO⁻Na⁺; COO⁻K⁺; [COO]₂Mg⁺²; [COO]₂Ca⁺²; mono and diCN at different positions; phenyl; CF₃; CO₃Me; CO₂D; CF₃; CO₂Me;benzo[d][1,3]dixol-5-yl; and difluorobenzo[d][1,3]dixol-5-yl.

Specific aspects of the invention include a deuterated compound selectedfrom the group consisting of:

2008 2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2008(R)(R)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2008(S)(S)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20142-amino-5-(3,4-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2014(R)(R)-2-amino-5-(3,4-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2014(S)(S)-2-amino-5-(3,4-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2017 methyl4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2017(R) methyl(R)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2017(S) methyl(S)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2018 methyl4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;2018(R) methyl(R)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;2018(S) methyl(S)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;2052 2-amino-5-(3-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2052(R)(R)-2-amino-5-(3-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2052(S)(S)-2-amino-5-(3-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20662-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2066(R)(R)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2066(S)(S)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2;

Related aspects of the invention include a pharmaceutical compositioncomprising a deuterated compound of Formulas {I-A} through {I-H}, notedabove, or a pharmaceutical acceptable salt thereof and apharmaceutically-acceptable carrier.

Related aspects of the invention include a pharmaceutical compositioncomprising a deuterated compound of Formulas {I-A} through {I-H}, notedabove or a pharmaceutical acceptable ester, metabolite, prodrug, orsolvate thereof and a pharmaceutically-acceptable carrier.

Related aspects of the invention include a pharmaceutical compositioncomprising a deuterated compound selected from the group consisting of aracemic, (R), and (S) named form of a compound, noted above or apharmaceutical acceptable salt thereof and a pharmaceutically-acceptablecarrier.

Related aspects of the invention include a pharmaceutical compositioncomprising a deuterated compound selected from the group consisting of aracemic, (R), and (S) named form of a compound, noted above or apharmaceutical acceptable ester, metabolite, prodrug, or solvate thereofand a pharmaceutically-acceptable carrier.

Other aspects of the invention relate to a method of treating orameliorating one or more conditions associated with a proliferativecellular disorder by administering one or more doses of a pharmaceuticalcomposition comprising one or more deuterated compounds in one or moreamounts effective to treat or ameliorate one or more conditionsassociated with the proliferative cellular disorder.

Related aspects of the invention include methods wherein saidproliferative cellular disorder is selected from the group consisting ofcancer, pancreatic cancer, lung cancer, breast cancer, glioblastomalcancer, neruobalstoma, osteosarcoma, ovarian cancer, cervical cancer,head and neck cancer, cholangiocarcinoma, and hepatocellular carcinoma.

Other related aspects of the invention relate to a method of treating orameliorating one or more conditions associated with hyperlipidemia,blood coagulation, complement activation and viral infections byadministering one or more doses of a pharmaceutical compositioncomprising one or more deuterated compounds in one or more amountseffective to treat or ameliorate one or more conditions associated withthe proliferative cellular disorder.

One aspect of the invention relates to a method of treatinghypercholesterolemia, comprising administering to a subject in needthereof, a therapeutically effective amount of a compound selected fromthe group consisting of one or more deuterated compounds in one or moreamounts effective to treat or ameliorate one or more conditionsassociated with hyperlipidemia.

One aspect of the invention relates to a method of treating a viraldisease, comprising administering to a subject in need thereof, atherapeutically effective amount of a compound selected from the groupconsisting of one or more deuterated compounds in one or more amountseffective to treat or ameliorate one or more conditions associated withviral disease.

One aspect also relates to a method wherein said viral disease isselected from the group consisting of hepatitis B, hepatitis C,hepatitis D, and human papillomavirus.

One aspect of the invention relates to a method of treating bloodcoagulation disorders, comprising administering to a subject in needthereof, a therapeutically effective amount of a compound selected fromthe group consisting of one or more deuterated compounds in one or moreamounts effective to treat or ameliorate one or more conditionsassociated with blood coagulation.

One aspect also relates to a method wherein said blood coagulationdisorder is selected from the group consisting of thrombosis, venousthrombosis, myocardial thrombosis, cerebral thrombosis, pulmonarythrombosis, and hepatic thrombosis.

Pharmaceutical Compositions

Related aspects of the invention are directed to compositions, includingpharmaceutical compositions, comprising the compounds of the invention,noted above. One aspect of the invention is directed to a pharmaceuticalcomposition comprising at least one pharmaceutically acceptableexcipient and a therapeutically effective amount of the compound or saltdisclosed above. Still another aspect of the invention relates to amethod for pharmaceutical formulation of previously described compoundsfor use in oral and intravenous applications, and in implantablematerials.

Another aspect of the present invention relates to a pharmaceuticalcomposition including a pharmaceutically acceptable carrier and acompound according to the aspects of the present invention. Thepharmaceutical composition can contain one or more of theabove-identified compounds of the present invention.

Typically, the pharmaceutical composition of the present invention willinclude a compound of the present invention or its pharmaceuticallyacceptable salt, as well as a pharmaceutically acceptable carrier. Theterm “pharmaceutically acceptable carrier” refers to any suitableadjuvants, carriers, excipients, or stabilizers, and can be in solid orliquid form such as, tablets, capsules, powders, solutions, suspensions,emulsions, or implantable disc.

Typically, the composition will contain from about 0.01 to 99 percent,preferably from about 20 to 75 percent of active compound(s), togetherwith the adjuvants, carriers and/or excipients. While individual needsmay vary, determination of optimal ranges of effective amounts of eachcomponent is within the skill of the art. Typical dosages comprise about0.01 to about 100 mg/kg body wt. The preferred dosages comprise about0.1 to about 100 mg/kg body wt. The most preferred dosages compriseabout 1 to about 100 mg/kg body wt. Treatment regimen for theadministration of the compounds of the present invention can also bedetermined readily by those with ordinary skill in art. That is, thefrequency of administration and size of the dose can be established byroutine optimization, preferably while minimizing any side effects.

Dosage Forms

The solid unit dosage forms can be of the conventional type. The solidform can be a capsule and the like, such as an ordinary gelatin typecontaining the compounds of the present invention and a carrier, forexample, lubricants and inert fillers such as, lactose, sucrose, orcornstarch. In another embodiment, these compounds are tabulated withconventional tablet bases such as lactose, sucrose, or cornstarch incombination with binders like acacia, cornstarch, or gelatin,disintegrating agents, such as cornstarch, potato starch, or alginicacid, and a lubricant, like stearic acid or magnesium stearate.

The tablets, capsules, and the like can also contain a binder such asgum tragacanth, acacia, corn starch, or gelatin; excipients such asdicakium phosphate; a disintegrating agent such as corn starch, potatostarch, alginic acid; a lubricant such as magnesium stearate; and asweetening agent such as sucrose, lactose, or saccharin. When the dosageunit form is a capsule, it can contain, in addition to materials of theabove type, a liquid carrier such as a fatty oil.

Optional Coatings

Various other materials may be present as coatings or to modify thephysical form of the dosage unit. For instance, tablets can be coatedwith shellac, sugar, or both. A syrup can contain, in addition to activeingredient, sucrose as a sweetening agent, methyl and propylparabens aspreservatives, a dye, and flavoring such as cherry or orange flavor.

Excipients

For oral therapeutic administration, these active compounds can beincorporated with excipients and used in the form of tablets, capsules,elixirs, suspensions, syrups, and the like. Such compositions andpreparations should contain at least 0.1% of active compound. Thepercentage of the compound in these compositions can, of course, bevaried and can conveniently be between about 2% to about 60% of theweight of the unit. The amount of active compound in suchtherapeutically useful compositions is such that a suitable dosage willbe obtained. Preferred compositions according to the present inventionare prepared so that an oral dosage unit contains between about 1 mg and800 mg of active compound.

Modes of Administration

The active compounds of the present invention may be orallyadministered, for example, with an inert diluent, or with an assailableedible carrier, or they can be enclosed in hard or soft shell capsules,or they can be compressed into tablets, or they can be incorporateddirectly with the food of the diet.

The pharmaceutical forms suitable for injectable use include sterileaqueous solutions or dispersions and sterile powders for theextemporaneous preparation of sterile injectable solutions ordispersions. In all cases, the form should be sterile and should befluid to the extent that easy syringability exists. It should be stableunder the conditions of manufacture and storage and should be preservedagainst the contaminating action of microorganisms, such as bacteria andfungi. The carrier can be a solvent or dispersion medium containing, forexample, water, ethanol, polyol (e.g., glycerol, propylene glycol, andliquid polyethylene glycol), suitable mixtures thereof, and vegetableoils.

The compounds or pharmaceutical compositions of the present inventionmay also be administered in injectable dosages by solution or suspensionof these materials in a physiologically acceptable diluent with apharmaceutical adjuvant, carrier or excipient. Such adjuvants, carriersand/or excipients include, but are not limited to, sterile liquids, suchas water and oils, with or without the addition of a surfactant andother pharmaceutically and physiologically acceptable components.Illustrative oils are those of petroleum, animal, vegetable, orsynthetic origin, for example, peanut oil, soybean oil, or mineral oil.In general, water, saline, aqueous dextrose and related sugar solution,and glycols, such as propylene glycol or polyethylene glycol, arepreferred liquid carriers, particularly for injectable solutions.

The pharmaceutical forms suitable for implantable use include sterilewafers of polycarboxyphenoxypropane-sebacic-acid (pCPP:SA) polymers,poly(D,L-lactic acid), polyhydroxybutyrate, lysine diisocyanate(LDI)-glycerol polyurethane, and poly(D-L lactide-co-glycolide). In allcases, the form should be sterile and should be a wafer or disc ofsuitable dimensions for surgical implantation in the brain. The polymersshould be stable under the conditions of manufacture and storage andshould be preserved against the contaminating action of microorganisms,such as bacteria and fungi. The wafers should be biodegradable in thecentral nervous system, and should permit the slow release of the abovementioned compounds, ranging from 24 hours up to 6 months. Such wafersmay be of particular value in enhancing the success of temporal lobeepilepsy surgery by suppressing persistent epileptogenic structures.

In one aspect, the invention provides compounds and compositions,including any aspect described herein, for use in any of the methods ofthis invention. In one aspect, use of a compound of this invention or acomposition comprising the same, will have utility in inhibiting,suppressing, enhancing or stimulating a desired response in a subject,as will be understood by one skilled in the art. In another embodiment,the compositions may further comprise additional active ingredients,whose activity is useful for the particular application for which thecompound of this invention is being administered.

Pharmaceutical Compositions Comprising Modulator Compounds of theInvention

Therapeutic compositions typically must be sterile and stable under theconditions of manufacture and storage. The composition can be formulatedas a solution, microemulsion, liposome, or other ordered structuresuitable to high drug concentration. The carrier can be a solvent ordispersion medium containing, for example, water, ethanol, polyol (forexample, glycerol, propylene glycol, and liquid polyethylene glycol, andthe like), and suitable mixtures thereof. The proper fluidity can bemaintained, for example, by the use of a coating such as lecithin, bythe maintenance of the required particle size in the case of dispersionand by the use of surfactants. In many cases, it will be preferable toinclude isotonic agents, for example, sugars, polyalcohols such asmannitol, sorbitol, or sodium chloride in the composition. Prolongedabsorption of the injectable compositions can be brought about byincluding in the composition an agent which delays absorption, forexample, monostearate salts and gelatin. Moreover, the modulators can beadministered in a time release formulation, for example in a compositionwhich includes a slow release polymer. The active compounds can beprepared with carriers that will protect the compound against rapidrelease, such as a controlled release formulation, including implantsand microencapsulated delivery systems. Biodegradable, biocompatiblepolymers can be used, such as ethylene vinyl acetate, polyanhydrides,polyglycolic acid, collagen, polyorthoesters, polylactic acid andpolylactic, polyglycolic copolymers (PLG). Many methods for thepreparation of such formulations are patented or generally known tothose skilled in the art.

The mode of administration may be oral, for intestinal delivery;intranasal, for nasal delivery; and intravenous for delivery through theblood-brain barrier. Other modes of administration as are known in theart may also be used, including, but not limited to intrathecal,intramuscular, intrabronchial, intrarectal, intraocular, andintravaginal delivery,

The modulator compounds can be administered as oral dosage compositionsfor small intestinal delivery. Such oral dosage compositions for smallintestinal delivery are well-known in the art, and generally comprisegastroresistent tablets or capsules (Remington's PharmaceuticalSciences, 16th Ed., Eds. Osol, Mack Publishing Co., Chapter 89 (1980);Digenis et al, J. Pharm. Sci., 83:915-921 (1994); Vantini et al, ClinicaTerapeutica, 145:445-451 (1993); Yoshitomi et al, Chem. Pharm. Bull.,40:1902′1905 (1992); Thoma et al, Pharmazie, 46:331-336 (1991);Morishita et al, Drug Design and Delivery, 7:309-319 (1991); and Lin etal, Pharmaceutical Res., 8:919-924 (1991)); each of which isincorporated by reference herein in its entirety).

Tablets are made gastroresistent by the addition of compounds such ascellulose acetate phthalate or cellulose acetate terephthalate.

Capsules are solid dosage forms in which the modulator compound isenclosed in either a hard or soft, soluble container or shell ofgelatin. The gelatin used in the manufacture of capsules is obtainedfrom collagenous material by hydrolysis. There are two types of gelatin.Type A, derived from pork skins by acid processing, and Type B, obtainedfrom bones and animal skins by alkaline processing. The use of hardgelatin capsules permit a choice in prescribing a modulator compound ora combination thereof at the exact dosage level considered best for theindividual subject. The hard gelatin capsule consists of two sections,one slipping over the other, thus completely surrounding the modulatorcompound. These capsules are filled by introducing the modulatorcompound, or gastroresistent beads containing the modulator compound,into the longer end of the capsule, and then slipping on the cap. Hardgelatin capsules are made largely from gelatin, FD&C colorants, andsometimes an opacifying agent, such as titanium dioxide. The USP permitsthe gelatin for this purpose to contain 0.15% (w/v) sulfur dioxide toprevent decomposition during manufacture.

In the context of the present invention, oral dosage compositions forsmall intestinal delivery also include liquid compositions which containaqueous buffering agents that prevent the modulator compound from beingsignificantly inactivated by gastric fluids in the stomach, therebyallowing the modulator compound to reach the small intestines in anactive form. Examples of such aqueous buffering agents which can beemployed in the present invention include bicarbonate buffer (pH 5.5 to8.7, preferably about pH 7.4).

When the oral dosage composition is a liquid composition, it ispreferable that the composition be prepared just prior to administrationso as to minimize stability problems. In this case, the liquidcomposition can be prepared by dissolving lyophilized modulator compoundin the aqueous buffering agent. Oral dosage compositions for smallintestinal delivery also include liquid compositions which mayoptionally contain aqueous buffering agents that prevent the therapeuticagent and modulator compound from being significantly inactivated bygastric fluids in the stomach, thereby allowing the biologically activeingredient and modulator compound to reach the small intestines in anactive form. Examples of such aqueous buffering agents which can beemployed in the present invention include bicarbonate buffer (pH 5.5 to8.7, preferably about pH 7.4).

When the oral dosage composition is a liquid composition, it ispreferable that the composition be prepared just prior to administrationso as to minimize stability problems. In this case, the liquidcomposition can be prepared by dissolving lyophilized therapeutic agentand modulator compound in the aqueous buffering agent.

Sterile injectable solutions can be prepared by incorporating the activecompound in the required amount in an appropriate solvent with one or acombination of ingredients enumerated above, as required, followed byfiltered sterilization. Generally, dispersions are prepared byincorporating the active compound into a sterile vehicle which containsa basic dispersion medium and the required other ingredients from thoseenumerated above. For sterile powders used in the preparation of sterileinjectable solutions, the preferred methods of preparation are vacuumdrying and freeze-drying which yields a powder of the active ingredientplus any additional desired ingredient from a previouslysterile-filtered solution thereof.

A “nasal” delivery composition differs from an “intestinal” deliverycomposition in that the latter must have gastroresistent properties inorder to prevent the acidic degradation of the active agents in thestomach, whereas the former generally comprises water-soluble polymerswith a diameter of about 50 μm order to reduce the mucociliaryclearance, and to achieve a reproducible bioavailability of the nasallyadministered agents.

An “intravenous” delivery composition differs from both the “nasal” and“intestinal” delivery compositions in that there is no need forgastroresistance or water-soluble polymers in the “intravenous” deliverycomposition.

Nasal dosage compositions for nasal delivery are well-known in the art.Such nasal dosage compositions generally comprise water-soluble polymersthat have been used extensively to prepare pharmaceutical dosage forms(Martin et al, In: Physical Chemical Principles of 20 PharmaceuticalSciences, 3rd Ed., pages 592-638 (1983)) that can serve as carriers forpeptides for nasal administration (Davis, In: Delivery Systems forPeptide Drugs, 125:1-21 (1986)). The nasal absorption of pap tidesembedded in polymer matrices has been shown to be enhanced throughretardation of nasal mucociliary clearance (Ilium et al, Int. J. Pharm,46:261-265 (1988). Other possible enhancement mechanisms include anincreased concentration gradient or decreased diffusion path forpeptides absorption (Ting et al, Pharm. Res., 9:1330-1335 (1992).However, reduction in mucociliary clearance rate has been predicted tobe a good approach toward achievement or reproducible bioavailability ofnasally administered systemic drugs (Gonda et al, Pharm. Res., 7:69-75(1990)). Microparticles with a diameter of about 50 pm are expected todeposit in the nasal cavity (Bjork et al, Int. J. Pharm., 62:187-192(1990); and Ilium et al, Int. J. Pharm., 39:189-199 (1987), whilemicroparticles with a diameter under 10 pm can escape the filteringsystem of the nose and deposit in the lower airways. Microparticleslarger than 200 pm in diameter will not be retained in the nose afternasal administration (Lewis et al, Proc. Int. Symp. Control Rel. Bioact.Mater., 17:280-290 (1990)).

The particular water-soluble polymer employed is not critical to thepresent invention, and can be selected from any of the well-knownwater-soluble polymers employed for nasal dosage forms. A typicalexample of a water-soluble polymer useful for nasal delivery ispolyvinyl alcohol (pvA). This material is a swellable hydrophilicpolymer whose physical properties depend on the molecular weight, degreeof hydrolysis, cross-linking density, and crystallinity (Peppas et al,In: Hydrogels in Medicine and Pharmacy, 3:109′131 (1987). PYA can beused in the coating of dispersed materials through phase separation,spray-drying, spray-embedding, and spray-densation (Ting et al, supra).

A “skin” delivery composition comprising a modulator compound of theinvention may include in addition a therapeutic or immunogenic agent,fragrance, creams, ointments, colorings, and other compounds so long asthe added component does not deleteriously affect transdermal deliveryof the therapeutic or immunogenic agent. Conventional pharmaceuticallyacceptable emulsifiers, surfactants, suspending agents, antioxidants,osmotic enhancers, extenders, diluents and preservatives may also beadded. Water soluble polymers can also be used as carriers.

The particular therapeutic or immunogenic agent employed is not criticalto the present invention, and can be, e.g., any drug compound,biologically active peptide, vaccine, or any other moiety otherwise notabsorbed through the transcellular pathway, regardless of size orcharge.

The amount of active compound in the composition may vary according tofactors such as the disease state, age, sex, and weight of theindividual. Dosage regimens may be adjusted to provide the optimumtherapeutic response. For example, a single bolus may be administered,several divided doses may be administered over time or the dose may beproportionally reduced or increased as indicated by the exigencies ofthe therapeutic situation. It is especially advantageous to formulateparenteral compositions in dosage unit form for ease of administrationand uniformity of dosage. Dosage unit form as used herein refers tophysically discrete units suited as unitary dosages for the mammaliansubjects to be treated; each unit containing a predetermined quantity ofactive compound calculated to produce the desired therapeutic effect inassociation with the required pharmaceutical carrier. The specificationfor the dosage unit forms of the invention are dictated by and directlydependent on (a) the unique characteristics of the active compound andthe particular therapeutic effect to be achieved, and (b) thelimitations inherent in the art of compounding such an active compoundfor the treatment of sensitivity in individuals.

As used herein “pharmaceutically-acceptable carrier” includes any andall solvents, dispersion media, coatings, antibacterial and antifungalagents, isotonic and absorption delaying agents, and the like that arephysiologically compatible. In one embodiment, the carrier is suitablefor parenteral administration. A carrier may be suitable foradministration into the central nervous system (e.g., intraspinally orintracerebrally). Alternatively, the carrier can be suitable forintravenous, intraperitoneal, or intramuscular administration. Inanother embodiment, the carrier is suitable for oral administration.Pharmaceutically-acceptable carriers include sterile aqueous solutionsor dispersions and sterile powders for the extemporaneous preparation ofsterile injectable solutions or dispersion. The use of such media andagents for pharmaceutically active substances is well known in the art.Except insofar as any conventional media or agent is incompatible withthe active compound, use thereof in the pharmaceutical compositions ofthe invention is contemplated. Supplementary active compounds can alsobe incorporated into the compositions.

Various Modifications and Alternatives, Generally

While specific aspects of the invention have been described in detail,it will be appreciated by those skilled in the art that variousmodifications and alternatives to those details could be developed inlight of the overall teachings of the disclosure. Accordingly, theparticular arrangements disclosed are meant to be illustrative only, andnot limiting as to the scope of the invention, which is to be given thefull breadth of the appended claims, and any equivalent, thereof.

EXAMPLES

The foregoing discussion may be better understood in connection with thefollowing representative examples which are presented for purposes ofillustrating the principle methods and compositions of the invention,and not by way of limitation. Various other examples will be apparent tothe person skilled in the art after reading the present disclosurewithout departing from the spirit and scope of the invention. It isintended that all such other examples be included within the scope ofthe appended claims.

General Materials and Methods

All parts are by weight (e.g., % w/w), and temperatures are in degreescentigrade (° C.), unless otherwise indicated. All reagents were fromSigma-Aldrich.

General Chemical Procedures

Melting points were determined with a Hoover melting point apparatus andare uncorrected.

Infrared (IR) spectra for the compounds were recorded in KBr discs on aMattson Satellite FTIR in cm⁻¹. ¹H and ¹³C spectra were recorded inDMSO-d on a Bruker Avance III DPX 300 MHz instrument. ¹⁹F spectra wererecorded in DMSO d, on a Bruker Avance III 600 (564.6 mHz). Chemicalshifts were expressed in parts per million with tetramethylsilane asinternal standard. Mass spectrometry was performed on a ThermoScientific LTQ-FT at the University of Cincinnati Mass Spectrometryfacility.

The purity of the compounds was monitored by HPLC using a Waters 2695separation module and a 2487 dual A absorbance detector with a NovaPakC18 4 μm 3.9×I 50 mm column. The mobile phases consisted ofacetonitrile/H20 using a 30 minute gradient. All compounds were 2:95%.

Microanalysis was performed by Atlantic Microlab Inc., and all compoundswere found to be ±0.4%.

Log S, Log P, Log BBB, human intestinal absorption, p-glycoproteincategory, CYP 2C9 pKi, hERG pIC50, CYP 2D6 affinity category, oral CNSscore, IV CNS score, MW, flexibility, and total polar surface area werecalculated using StarDrop 5.1.1 release Build 178.

FIGS. 3, 4, 5, 6, and 7 illustrate the mechanism of action and syntheticreactions used to prepare unlabeled or isotopically stabilizedtetronimide modulator compounds comprising one or more deuterium atoms.

FIG. 4 illustrates the mechanism of action of tetronimide modulatingcompounds. Deuterium can stabilize a stereo-center, or can be used toslow down or suppress metabolism. Compound #2066 has a deuterium at thestereocenter, as well as two deuteriums at the benzylic positionadjacent to the “C” ring. Compound #2084 has two deuteriums on the aminoof the tetronimide ring. Compound #2085 has a deuterium at thestereocenter, two deuteriums at the benzylic position adjacent to the“C” ring, and two deuteriums on the amino of the tetronimide ring.Compound #1072 has two deuteriums at the benzylic position adjacent tothe “C” ring, and the “C” ring is perdeuterated. Compound #2087 isdeuterated at the stereocenter, the benzylic position adjacent to the“C” ring, two deuteriums on the amine of the tetronimide, and the “C”ring is perdeuterated. Compound #1084 has the “A” ring perdeuterated.

FIG. 5 illustrates the synthesis of non-deuterated ASPH modulators inScheme 1. Scheme 2 illustrates the synthesis of compounds of the formula{I-A} and {I-B}. Scheme 3 illustrates the synthesis of compounds of theformula {I-D} Scheme 4 illustrates the synthesis of compounds of theformula {I-E}.

FIG. 6 illustrates an alternate synthesis of compounds of the formula{I-D} in Scheme 5. Scheme 6 illustrates the synthesis of perdeuteratedphenylmethanesulfonyl chloride. Scheme 7 illustrates the synthesis ofcompounds of the formula {I-F}.

FIG. 7 illustrates the synthesis of compounds of the formula {I-G} inScheme 8. Scheme 9 illustrates the synthesis of compounds of the formula{I-G}. Scheme 10 illustrates the synthesis of compounds of the formula{I-H}.

FIGS. 10-1 to 10-62 illustrate NMR spectra of unlabeled precursorcompounds, particularly multiple peaks for specific compounds, eachcompound given an MO-I number, which can be cross-correlated withcurrent numbers, names, and structures of the #1000 series of compoundslisted in Table 3.

Table 1 is a non-limiting list of unsubstituted and substituted arylfunctional groups that can be incorporated into compounds of theinvention represented by Formulas noted within the text and embedded orsupplemental tables of the specification, the figures, and the claims.

TABLE 1 A Non-Limiting List of Aryl Functional Groups That Can BeIncorporated Formulas of the Invention Functional Group No StructureAryl Name a

phenyl b

2-fluorophenyl c

3-fluorophenyl d

4-fluorophenyl e

2-chlorophenyl f

3-chlorophenyl g

4-chlorophenyl h

2-bromophenyl i

3-bromophenyl j

4-bromophenyl k

2-iodophenyl l

3-iodophenyl m

4-iodophenyl n

2-trifluoromethylphenyl o

3-trifluoromethylphenyl p

4-trifluoromethylphenyl q

2-benzoic acid r

3-benzoic acid s

4-benzoic acid t

2-carboxymethylphenyl u

3-carboxymethylphenyl v

4-carboxymethylphenyl w

2-methoxyphenyl x

3-methoxyphenyl y

4-methoxyphenyl z

2-carboxyethylphenyl aa

3-carboxyethylphenyl ab

4-carboxyethylphenyl ac

2-nitrilephenyl ad

3-nitrilephenyl ae

4-nitrilephenyl af

2-sulfonamidophenyl ag

3-sulfonamidophenyl ah

4-sulfonamidophenyl ai

2,3-difluorophenyl aj

2,4-difluorophenyl ak

2,5-difluorophenyl al

2,6-difluorophenyl am

3,4-difluorophenyl an

3,5-difluorophenyl ap

2,3-dichlorophenyl aq

2,4-dichlorophenyl ar

2,5-dichlorophenyl as

2,6-dichlorophenyl at

3,4-dichlorophenyl au

3,5-dichlorophenyl av

2-chloro-3-fluorophenyl aw

2-chloro-4-fluorophenyl ax

2-chloro-5-fluorophenyl ay

2-chloro-6-fluorophenyl az

3-chloro-2-fluorophenyl ba

3-chloro-4-fluorophenyl bb

3-chloro-5-fluorophenyl bc

3-chloro-6-fluorophenyl bd

4-chloro-2-fluorophenyl be

4-chloro-3-fluorophenyl bf

2,3-methylenedioxyphenyl bg

3,4-methylenedioxyphenyl bh

2,3-difluoromethylenedioxyphenyl bi

3,4-difluoromethylenedioxyphenyl bj

Methyl-phenyl acetate bk

N-2-phenyl-methanesulfonamide bl

N-3-phenyl-methanesulfonamide bm

N-4-phenyl-methanesulfonamide bn

2-acetylphenyl bo

3-acetylphenyl bp

4-acetylphenyl bq

4-carboxymethyl-2-fluorophenyl br

4-carboxymethyl-3-fluorophenyl bs

4-carboxymethyl-2,3-difluorophenyl bt

4-carboxymethyl-3,5-difluorophenyl bu

4-carboxymethyl-2,3,5-trifluorophenyl by

4-carboxymethyl-2,3,5,6-tetrafluorophenyl bw

4-carboxymethyl-2-chlorophenyl bx

4-carboxymethyl-3-chlorophenyl by

4-carboxymethyl-3-chloro-2-fluorophenyl bz

4-carboxymethyl-2-chloro-3-fluorophenyl ca

4-carboxymethyl-3-chloro-5-fluorophenyl cb

4-carboxymethyl-2-methoxyphenyl cc

4-carboxymethyl-3-methoxyphenyl cd

4-carboxymethyl-2-bromophenyl ce

4-carboxymethyl-3-bromophenyl cf

2-fluoro-4-benzoic acid cg

3-fluoro-4-benzoic acid ch

2,3-difluoro-4-benzoic acid ci

3,5-difluoro-4-benzoic acid cj

2,3,5-trifluoro-4-benzoic acid ck

2,3,5,6-tetrafluoro-4-benzoic acid cl

2-chloro-4-benzoic acid cm

3-chloro-4-benzoic acid cn

3-chloro-2-fluoro-4-benzoic acid co

2-chloro-3-fluoro-4-benzoic acid cp

3-chloro-5-fluoro-4-benzoic acid cq

2-methoxy-4-benzoic acid cr

3-methoxy-4-benzoic acid cs

2-bromo-4-benzoic acid ct

3-bromo-4-benzoic acid

Example 1—Unlabeled Tetronimide Compounds (#1001-1079) Synthesis ofExemplary Unlabeled Tetronimide Compounds

Table 2 provides a list illustrating the structures, names, and numbersof a variety of key compounds disclosed in this example.

Synthesis of exemplary compounds are described in one or more sectionsfollowing the tables noted below.2-(aryl)-4-hydroxy-5-amino-3(2H)furanones are prepared according to themethod of Dahn (Experientia (1954), 10, 245-6). Sulfonylated compoundsare prepared according to U.S. Pat. No. 9,771,356.

TABLE 2 (#1001-1083) Structures, Names, and Numbers of Key UnlabeledCompounds Listed in Example 1 CP# Structure Name Formula MW 1001

2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl methanesulfonateC₁₁H₁₀ClNO₅S 303.71 1002

2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl ethanesulfonateC₁₂H₁₂ClNO₅S 317.74 1003

2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-ylpropane-1-sulfonate C₁₃H₁₄ClNO₅S 331.77 1004

2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-ylpropane-2-sulfonate C₁₃H₁₄ClNO₅S 331.77 1005

2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-ylbutane-1-sulfonate C₁₄H₁₆ClNO₅S 345.79 1006

2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl2-methylpropane-1- sulfonate C₁₄H₁₆ClNO₅S 345.79 1008

2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₄ClNO₅S 379.81 1009

2-amino-5-(2-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₄ClNO₅S 379.81 1010

2-amino-5-(3-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₄ClNO₅S 379.81 1011

2-amino-5-(2,3- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₃Cl₂NO₅S 414.25 1012

2-amino-5-(2,4- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₃Cl₂NO₅S 414.25 1013

2-amino-5-(2,5- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₃Cl₂NO₅S 414.25 1014

2-amino-5-(3,4- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₃Cl₂NO₅S 414.25 1015

2-amino-5-(3,5- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₃Cl₂NO₅S 414.25 1016

methyl 3-(5-amino-4- ((benzylsulfonyl)oxy)-3-oxo- 2,3-dihydrofuran-2-yl)benzoate C₁₉H₁₇NO₇S 403.40 1017

methyl 4-(5-amino-4- ((benzylsulfonyl)oxy)-3-oxo- 2,3-dihydrofuran-2-yl)benzoate C₁₉H₁₇NO₇S 403.40 1018

methyl 4-(5-amino-4- ((benzylsulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl)-2- fluorobenzoate C₁₉H₁₆FNO₇S 421.40 1019

ethyl 4-(5-amino-4- ((benzylsulfonyl)oxy)-3-oxo- 2,3-dihydrofuran-2-yl)benzoate C₂₀H₁₉NO₇S 417.43 1020

5-(4-acetylphenyl)-2-amino- 4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate C₁₉H₁₇NO₆S 387.41 1021

2-amino-5-(4- carbamoylphenyl)-4-oxo- 4,5-dihydrofuran-3-ylphenylmethanesulfonate C₁₈H₁₆N₂O₆S 388.39 1022

4-(5-amino-4- ((benzylsulfonyl)oxy)-3-oxo- 2,3-dihydrofuran-2-yl)benzoic acid C₁₈H₁₅NO₇S 389.38 1027

2-amino-5-(2-fluorophenyl)- 4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₄FNO₅S 363.36 1028

2-amino-5-(3-fluorophenyl)- 4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₄FNO₅S 363.36 1029

2-amino-5-(4-fluorophenyl)- 4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₄FNO₅S 363.36 1030

2-amino-5-(2,3- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₃F₂NO₅S 381.35 1031

2-amino-5-(2,4- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₃F₂NO₅S 381.35 1032

2-amino-5-(2,5- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₃F₂NO₅S 381.35 1033

2-amino-5-(2,6- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₃F₂NO₅S 381.35 1034

2-amino-5-(3,4- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₃F₂NO₅S 381.35 1035

2-amino-5-(3,5- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₃F₂NO₅S 381.35 1036

2-amino-5-(2- methoxyphenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₈H₁₇NO₆S 375.39 1037

2-amino-5-(3- methoxyphenyl)-4-oxo-4,5 dihydrofuran-3-ylphenylmethanesulfonate C₁₈H₁₇NO₆S 375.39 1038

2-amino-5-(4- methcxyphenyl)-4-oxo-4,5 dihydrofuran-3-ylphenylmethanesulfonate C₁₈H₁₇NO₆S 375.39 1039

2-amino-5-(2,3- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-ylphenylmethanesulfonate C₁₉H₁₉NO₇S 405.42 1040

2-amino-5-(2,4- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-ylphenylmethanesulfonate C₁₉H₁₉NO₇S 405.42 1041

2-amino-5-(2,5- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-ylphenylmethanesulfonate C₁₉H₁₉NO₇S 405.42 1042

2-amino-5-(2,6- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-ylphenylmethanesulfonate C₁₉H₁₉NO₇S 405.42 1043

2-amino-5-(3,4- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-ylphenylmethanesulfonate C₁₉H₁₉NO₇S 405.42 1044

2-amino-5-(3,5- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-ylphenylmethanesulfonate C₁₉H₁₉NO₇S 405.42 1045

2-amino-5-(2-bromophenyl)- 4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₄BrNO₅S 424.27 1046

2-amino-5-(3-bromophenyl)- 4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₄BrNO₅S 424.27 1047

2-amino-5-(4-bromophenyl)- 4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₄BrNO₅S 424.27 1048

2-amino-5-(2-chloro-3- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₃ClFNO₅S 397.80 1049

2-amino-5-(2-chloro-4- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₃ClFNO₅S 397.80 1050

2-amino-5-(2-chloro-5- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₃ClFNO₅S 397.80 1051

2-amino-5-(2-chloro-6- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₃ClFNO₅S 397.80 1052

2-amino-5-(3-chloro-2- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₃ClFNO₅S 397.80 1053

2-amino-5-(3-chloro-4- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₃ClFNO₅S 397.80 1054

2-amino-5-(3-chloro-5- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₃ClFNO₅S 397.80 1055

2-amino-5-(5-chloro-2- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₃ClFNO₅S 397.80 1056

2-amino-5-(4-chloro-2- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₃ClFNO₅S 397.80 1057

2-amino-5-(4-chloro-3- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₃ClFNO₅S 397.80 1058

2-amino-4-oxo-5-(o-tolyl)- 4,5-dihydrofuran-3-yl phenylmethanesulfonateC₁₈H₁₇NO₅S 359.40 1059

2-amino-4-oxo-5-(m-tolyl)- 4,5-dihydrofuran-3-yl phenylmethanesulfonateC₁₈H₁₇NO₅S 359.40 1060

2-amino-4-oxo-5-(p-tolyl)- 4,5-dihydrofuran-3-yl phenylmethanesulfonateC₁₈H₁₇NO₅S 359.40 1061

2-amino-5-(3-cyanophenyl)- 4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate C₁₈H₁₄N₂O₅S 370.38 1062

2-amino-5-(4-cyanophenyl)- 4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate C₁₈H₁₄N₂O₅S 370.38 1063

2-amino-4-oxo-5-phenyl-4,5- dihydrofuran-3-yl phenylmethanesulfonateC₁₇H₁₅NO₅S 345.37 1064

2-amino-4-oxo-5-(2- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₈H₁₄F₃NO₅S 413.37 1065

2-amino-4-oxo-5-(3- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₈H₁₄F₃NO₅S 413.37 1066

2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₈H₁₄F₃NO₅S 413.37 1067

2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl(4-fluorophenyl) methanesulfonate C₁₈H₁₃F₄NO₅S 431.36 1068

methyl 4-(5-amino-4-(((4- fluorobenzyl)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2- yl)benzoate C₁₉H₁₆FNO₇S 421.40 1069

ethyl 4-(5-amino-4-(((4- fluorobenzyl)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2- yl)benzoate C₂₀H₁₈FNO₇S 435.42 1070

4-(5-amino-4-(((4- fluorobenzyl)sulfonyl)oxy)-3- oxo-2,3-dihydrofuran-2-yl)benzoic acid C₁₈H₁₄FNO₇S 407.37 1071

methyl 4-(5-amino-4-(((4- fluorobenzyl)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl)- 2-fluorobenzoate C₁₉H₁₅F₂NO₇S 439.39 1077

2-amino-5- (benzo[d][1,3]dioxol-5-yl)-4- oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate C₁₈H₁₅NO₇S 389.38 1078

2-amino-5-(2,2- difluorobenzo[d][1,3]dioxol- 5-yl)-4-oxo-4,5-dihydrofuran-3-yl phenylmethanesulfonate C₁₈H₁₃F₂NO₇S 425.36 1079

methyl 2-(4-(5-amino-4- ((benzylsulfonyl)oxy)-3-oxo- 2,3-dihydrofuran-2-yl)phenyl)acetate C₂₀H₁₉NO₇S 417.43 1081

2-amino-4-oxo-5-(6- (trifluoromethyl)pyridin-3-yl)-4,5-dihydrofuran-3-yl phenylmethanesulfonate C₁₇H₁₃F₃N₂O₅S 414.361082

2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl(4-chlorophenyl) methanesulfonate C₁₈H₁₃ClF₃NO₅S 447.81 1083

2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl(4-(trifluoromethyl)phenyl) methanesulfonate C₁₉H₁₃F₆NO₅S 481.37

TABLE 3 Compounds by Informal Number and Chemical Name with NMR SpectraCP # Structure and Informal Name Chemical Name Formula Mol Wt 1010

2-amino-5-(3-chlorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₄ClNO₅S 379.81 1029

2-amino-5-(4-fluorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₄FNO₅S 363.36 1028

2-amino-5-(3-fluorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₄FNO₅S 363.36 1027

2-amino-5-(2-fluorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₄FNO₅S 363.36 1030

2-amino-5-(2,3-difluorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₃F₂NO₅S 381.35 1034

2-amino-5-(3,4-difluorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₃F₂NO₅S 381.35 1031

2-amino-5-(2,4-difluorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₃F₂NO₅S 381.35 1035

2-amino-5-(3,5-difluorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₃F₂NO₅S 381.35 1011

2-amino-5-(2,3-dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₃Cl₂NO₅S 414.25 1014

2-amino-5-(3,4-dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₃Cl₂NO₅S 414.25 1062

2-amino-5-(4-cyanophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₈H₁₄N₂O₅S 370.38 1066

2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₈H₁₄F₃NO₅S 413.37 1047

2-amino-5-(4-bromophenyl)-4-oxo-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₇H₁₄BrNO₅S 424.27 2081

2-amino-4-oxo-5-(6- (trifluoromethyl)pyridin-3-yl)-4,5-dihydrofuran-3-yl phenylmethanesulfonate C17H13F3N2O5S 414.36 1017

methyl 4-(5-amino-4- ((benzylsulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl)benzoate C₁₉H₁₇NO₇S 403.40 1077

2-amino-5-(benzo[d][1,3]dioxol-5-yl)-4- oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate C₁₈H₁₅NO₇S 389.38 1078

2-amino-5-(2,2- difluorobenzo[d][1,3]dioxol-5-yl)-4-oxo-4,5-dihydrofuran-3-yl phenylmethanesulfonate C₁₈H₁₃F₂NO₇S 425.36 1079

methyl 2-(4-(5-amino-4- ((benzylsulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl)phenyl)acetate C₂₀H₁₉NO₇S 417.43 2082

2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl (4-chlorophenyl)methanesulfonate C₁₈H₁₃ClF₃NO₅S 447.81 2067

2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl (4-fluorophenyl)methanesulfonate C₁₈H₁₃F₄NO₅S 431.36 2083

2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl (4-(trifluoromethyl)phenyl)methanesulfonate C₁₉H₁₃F₆NO₅S 481.37

Example 2—Isotopically-Stabilized (Deuterated) Tetronimide Compounds(#2001-2093) Synthesis of Exemplary Isotopically-Stabilized TetronimideCompounds

Synthesis of exemplary isotopically-stabilized (deuterated) compoundsare described below.

Compounds of the class designated as2-(aryl)-4-hydroxy-5-amino-3(2H)furanones are prepared according to themethod of Dahn (Experientla (1954), 10, 245-6).

Sulfonylated compounds are prepared according to U.S. Pat. No.9,771,356.

TABLE 4 (Selected #1000 series and #20001-2093) Structures, Names, andNumbers of Key Isoptopically-Stabalized Tetronimide Compounds Listed inExample 2 New# Structure Name Formula MW 1007

2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-ylbenzenesulfonate-d5 C₁₆H₇D₅ClNO₅S 370.81 1072

2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl(phenyl- d5)methanesulfonate-d2 C₁₈H₇D₇F₃NO₅S 420.411073

methyl 4-(5-amino-3-oxo-4- ((((phenyl-d5)methyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl)benzoate C₁₉H₁₀D₇NO₇S 410.45 1074

ethyl 4-(5-amino-3-oxo-4- ((((phenyl-d5)methyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl)benzoate C₂₀H₁₂D₇NO₇S 424.47 1075

4-(5-amino-3-oxo-4- ((((phenyl-d5)methyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl)benzoic acid C₁₈H₈D₇NO₇S 396.42 1076

methyl 4-(5-amino-3-oxo-4- ((((phenyl-d5)methyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl)-2- fluorobenzoate C₁₉H₉D₇FNO₇S 428.44 1084

2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5-dihydrofuran-3-yl phenylmethanesulfonate C₁₈H₁₀D₄F₃NO₅S 417.39 1085

2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5-dihydrofuran-3-yl(phenyl- d5)methanesulfonate C₁₈H₅D₉F₃NO₅S 422.42 2001

2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-dmethanesulfonate-d3 C₁₁H₆D₄ClNO₅S 307.74 2001(R)

(R)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dmethanesulfonate-d3 C₁₁H₆D₄ClNO₅S 307.74 2001(S)

(S)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dmethanesulfonate-d3 C₁₁H₆D₄ClNO₅S 307.74 2002

2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-dethane-1-sulfonate-1,1- d2 C₁₂H₉D₃ClNO₅S 320.76 2002(R)

(R)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dethane-1-sulfonate-1,1-d2 C₁₂H₉D₃ClNO₅S 320.76 2002(S)

(S)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dethane-1-sulfonate-1,1-d2 C₁₂H₉D₃ClNO₅S 320.76 2003

2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-dpropane-1-sulfonate- 1,1-d2 C₁₃H₁₁D₃ClNO₅S 334.79 2003(R)

(R)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dpropane-1-sulfonate-1,1-d2 C₁₃H₁₁D₃ClNO₅S 334.79 2003(S)

(S)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dpropane-1-sulfonate-1,1-d2 C₁₃H₁₁D₃ClNO₅S 334.79 2004

2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-dpropane-2-sulfonate-2-d C₁₃H₁₂D₂ClNO₅S 333.78 2004(R)

(R)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dpropane-2-sulfonate-2-d C₁₃H₁₂D₂ClNO₅S 333.78 2004(S)

(S)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dpropane-2-sulfonate-2-d C₁₃H₁₂D₂ClNO₅S 333.78 2005

2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-dbutane-1-sulfonate-1,1- d2 C₁₄H₁₃D₃ClNO₅S 348.81 2005(R)

(R)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dbutane-1-sulfonate-1,1-d2 C₁₄H₁₃D₃ClNO₅S 348.81 2005(S)

(S)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dbutane-1-sulfonate-1,1-d2 C₁₄H₁₃D₃ClNO₅S 348.81 2006

2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-d2-methylpropane-1- sulfonate-1,1-d2 C₁₄H₁₃D₃ClNO₅S 348.81 2006(R)

(R)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d 2-methylpropane-1-sulfonate- 1,1-d2 C₁₄H₁₃D₃ClNO₅S 348.81 2006(S)

(S)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-d 2-methylpropane-1-sulfonate- 1,1-d2 C₁₄H₁₃D₃ClNO₅S 348.81 2007

2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-dbenzenesulfonate C₁₆H₁₁DClNO₅S 366.79 2007(R)

(R)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dbenzenesulfonate C₁₆H₁₁DClNO₅S 366.79 2007(S)

(S)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dbenzenesulfonate C₁₆H₁₁DClNO₅S 366.79 2008

2-amino-5-(4-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-dphenylmethanesulfonate-d2 C₁₇H₁₁D₃ClNO₅S 382.83 2008(R)

(R)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₁D₃ClNO₅S 382.83 2008(S)

(S)-2-amino-5-(4- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₁D₃ClNO₅S 382.83 2009

2-amino-5-(2-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-dphenylmethanesulfonate-d2 C₁₇H₁₁D₃ClNO₅S 382.83 2009(R)

(R)-2-amino-5-(2- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₁D₃ClNO₅S 382.83 2009(S)

(S)-2-amino-5-(2- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₁D₃ClNO₅S 382.83 2010

2-amino-5-(3-chlorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-dphenylmethanesulfonate-d2 C₁₇H₁₁D₃ClNO₅S 382.83 2010(R)

(R)-2-amino-5-(3- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₁D₃ClNO₅S 382.83 2010(S)

(S)-2-amino-5-(3- chlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₁D₃ClNO₅S 382.83 2011

2-amino-5-(2,3- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃Cl₂NO₅S 417.27 2011(R)

(R)-2-amino-5-(2,3- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃Cl₂NO₅S 417.27 2011(S)

(S)-2-amino-5-(2,3- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃Cl₂NO₅S 417.27 2012

2-amino-5-(2,4- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃Cl₂NO₅S 417.27 2012(R)

(R)-2-amino-5-(2,4- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃Cl₂NO₅S 417.27 2012(S)

(S)-2-amino-5-(2,4- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃Cl₂NO₅S 417.27 2013

2-amino-5-(2,5- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃Cl₂NO₅S 417.27 2013(R)

(R)-2-amino-5-(2,5- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃Cl₂NO₅S 417.27 2013(S)

(S)-2-amino-5-(2,5- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃Cl₂NO₅S 417.27 2014

2-amino-5-(3,4- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃Cl₂NO₅S 417.27 2014(R)

(R)-2-amino-5-(3,4- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃Cl₂NO₅S 417.27 2014(S)

(S)-2-amino-5-(3,4- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃Cl₂NO₅S 417.27 2015

2-amino-5-(3,5- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃Cl₂NO₅S 417.27 2015(R)

(R)-2-amino-5-(3,5- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃Cl₂NO₅S 417.27 2015(S)

(S)-2-amino-5-(3,5- dichlorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃Cl₂NO₅S 417.27 2016

methyl3-(5-amino-3-oxo-4- (((phenylmethyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2- d)benzoate C₁₉H₁₄D₃NO₇S 406.42 2016(R)

methyl (R)-3-(5-amino-3- oxo-4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2- d)benzoate C₁₉H₁₄D₃NO₇S 406.42 2016(S)

methyl (S)-3-(5-amino-3- oxo-4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2- d)benzoate C₁₉H₁₄D₃NO₇S 406.42 2017

methyl 4-(5-amino-3-oxo-4 (((phenylmethyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2- d)benzoate C₁₉H₁₄D₃NO₇S 406.42 2017(R)

methyl (R)-4-(5-amino-3- oxo-4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2- d)benzoate C₁₉H₁₄D₃NO₇S 406.42 2017(S)

methyl (S)-4-(5-amino-3- oxo-4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2- d)benzoate C₁₉H₁₄D₃NO₇S 406.42 2018

methyl 4-(5-amino-3-oxo-4 (((phenylmethyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)-2- fluorobenzoate C₁₉H₁₃D₃FNO₇S 424.41 2018(R)

methyl (R)-4-(5-amino-3- oxo-4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)-2- fluorobenzoate C₁₉H₁₃D₃FNO₇S 424.41 2018(S)

methyl (S)-4-(5-amino-3- oxo-4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)-2- fluorobenzoate C₁₉H₁₃D₃FNO₇S 424.41 2019

ethyl 4-(5-amino-3-oxo-4- (((phenylmethyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2- d)benzoate C₂₀H₁₆D₃NO₇S 420.45 2019(R)

ethyl (R)-4-(5-amino-3-oxo- 4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2- d)benzoate C₂₀H₁₆D₃NO₇S 420.45 2019(S)

ethyl (S)-4-(5-amino-3-oxo- 4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2- d)benzoate C₂₀H₁₆D₃NO₇S 420.45 2020

5-(4-acetylphenyl)-2-amino- 4-oxo-4,5-dihydrofuran-3-yl- 5-dphenylmethanesulfonate-d2 C₁₉H₁₄D₃NO₆S 390.42 2020(R)

(R)-5-(4-acetylphenyl)-2- amino-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₉H₁₄D₃NO₆S 390.42 2020(S)

(S)-5-(4-acetylphenyl)-2- amino-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₉H₁₄D₃NO₆S 390.42 2021

2-amino-5-(4- carbamoylphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₈H₁₃D₃N₂O₆S 391.41 2021(R)

(R)-2-amino-5-(4- carbamoylphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₈H₁₃D₃N₂O₆S 391.41 2021(S)

(S)-2-amino-5-(4- carbamoylphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₈H₁₃D₃N₂O₆S 391.41 2022

4-(5-amino-3-oxo-4- (((phenylmethyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2- d)benzoic acid-d C₁₈H₁₁D₄NO₇S 393.40 2022(R)

(R)-4-(5-amino-3-oxo-4- (((phenylmethyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2- d)benzoic acid-d C₁₈H₁₁D₄NO₇S 393.40 2022(S)

(S)-4-(5-amino-3-oxo-4- (((phenylmethyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2- d)benzoic acid-d C₁₈H₁₁D₄NO₇S 393.40 2023

sodium4-(5-amino-3-oxo-4 (((phenylmethyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2- d)benzoate C₁₈H₁₁D₃NNaO₇S 414.38 2023(R)

sodium(R)-4-(5-amino-3- oxo-4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2- d)benzoate C₁₈H₁₁D₃NNaO₇S 414.38 2023(S)

sodium(S)-4-(5-amino-3- oxo-4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2- d)benzoate C₁₈H₁₁D₃NNaO₇S 414.38 2024

potassium 4-(5-amino-3- oxo-4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2- d)benzoate C₁₈H₁₁D₃KNO₇S 430.49 2024(R)

potassium(R)-4-(5-amino-3 oxo-4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2- d)benzoate C₁₈H₁₁D₃KNO₇S 430.49 2024(S)

potassium(S)-4-(5-amino-3 oxo-4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2- d)benzoate C₁₈H₁₁D₃KNO₇S 430.49 2027

2-amino-5-(2-fluorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-dphenylmethanesulfonate-d2 C₁₇H₁₁D₃FNO₅S 366.38 2027(R)

(R)-2-amino-5-(2- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₁D₃FNO₅S 366.38 2027(S)

(S)-2-amino-5-(2- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₁D₃FNO₅S 366.38 2028

2-amino-5-(3-fluorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-dphenylmethanesulfonate-d2 C₁₇H₁₁D₃FNO₅S 366.38 2028(R)

(R)-2-amino-5-(3- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₁D₃FNO₅S 366.38 2028(S)

(S)-2-amino-5-(3- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₁D₃FNO₅S 366.38 2029

2-amino-5-(4-fluorophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-dphenylmethanesulfonate-d2 C₁₇H₁₁D₃FNO₅S 366.38 2029(R)

(R)-2-amino-5-(4- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₁D₃FNO₅S 366.38 2029(S)

(S)-2-amino-5-(4- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₁D₃FNO₅S 366.38 2030

2-amino-5-(2,3- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃F₂NO₅S 384.37 2030(R)

(R)-2-amino-5-(2,3- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃F₂NO₅S 384.37 2030(S)

(S)-2-amino-5-(2,3- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃F₂NO₅S 384.37 2031

2-amino-5-(2,4- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃F₂NO₅S 384.37 2031(R)

(R)-2-amino-5-(2,4- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃F₂NO₅S 384.37 2031(S)

(S)-2-amino-5-(2,4- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃F₂NO₅S 384.37 2032

2-amino-5-(2,5- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃F₂NO₅S 384.37 2032(R)

(R)-2-amino-5-(2,5- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃F₂NO₅S 384.37 2032(S)

(S)-2-amino-5-(2,5- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃F₂NO₅S 384.37 2033

2-amino-5-(2,6- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃F₂NO₅S 384.37 2033(R)

(R)-2-amino-5-(2,5- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃F₂NO₅S 384.37 2033(S)

(S)-2-amino-5-(2,6- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃F₂NO₅S 384.37 2034

2-amino-5-(3,4- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃F₂NO₅S 384.37 2034(R)

(R)-2-amino-5-(3,4- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃F₂NO₅S 384.37 2034(S)

(S)-2-amino-5-(3,4- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃F₂NO₅S 384.37 2035

2-amino-5-(3,5- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃F₂NO₅S 384.37 2035(R)

(R)-2-amino-5-(3,5- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃F₂NO₅S 384.37 2035(S)

(S)-2-amino-5-(3,5- difluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃F₂NO₅S 384.37 2036

2-amino-5-(2- methoxyphenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₈H₁₄D₃NO₆S 378.41 2036(R)

(R)-2-amino-5-(2- methoxyphenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₈H₁₄D₃NO₆S 378.41 2036(S)

(S)-2-amino-5-(2- methoxyphenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₈H₁₄D₃NO₆S 378.41 2037

2-amino-5-(3- methoxyphenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₈H₁₄D₃NO₆S 378.41 2037(R)

(R)-2-amino-5-(3- methoxyphenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₈H₁₄D₃NO₆S 378.41 2037(S)

(S)-2-amino-5-(3- methoxyphenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₈H₁₄D₃NO₆S 378.41 2038

2-amino-5-(4- methoxyphenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₈H₁₄D₃NO₆S 378.41 2038(R)

(R)-2-amino-5-(4- methoxyphenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₈H₁₄D₃NO₆S 378.41 2038(S)

(S)-2-amino-5-(4- methoxyphenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₈H₁₄D₃NO₆S 378.41 2039

2-amino-5-(2,3- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₉H₁₆D₃NO₇S 408.44 2039(R)

(R)-2-amino-5-(2,3- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₉H₁₆D₃NO₇S 408.44 2039(S)

(S)-2-amino-5-(2,3- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₉H₁₆D₃NO₇S 408.44 2040

2-amino-5-(2,4- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₉H₁₆D₃NO₇S 408.44 2040(R)

(R)-2-amino-5-(2,4- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₉H₁₆D₃NO₇S 408.44 2040(S)

(S)-2-amino-5-(2,4- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₉H₁₆D₃NO₇S 408.44 2041

2-amino-5-(2,5- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₉H₁₆D₃NO₇S 408.44 2041(R)

(R)-2-amino-5-(2,5- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₉H₁₆D₃NO₇S 408.44 2041(S)

(S)-2-amino-5-(2,5- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₉H₁₆D₃NO₇S 408.44 2042

2-amino-5-(2,6- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₉H₁₆D₃NO₇S 408.44 2042(R)

(R)-2-amino-5-(2,6- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₉H₁₆D₃NO₇S 408.44 2042(S)

(S)-2-amino-5-(2,5- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₉H₁₆D₃NO₇S 408.44 2043

2-amino-5-(3,4- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₉H₁₆D₃NO₇S 408.44 2043(R)

(R)-2-amino-5-(3,4- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₉H₁₆D₃NO₇S 408.44 2043(S)

(S)-2-amino-5-(3,4- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₉H₁₆D₃NO₇S 408.44 2044

2-amino-5-(3,5- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₉H₁₆D₃NO₇S 408.44 2044(R)

(R)-2-amino-5-(3,5- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₉H₁₆D₃NO₇S 408.44 2044(S)

(S)-2-amino-5-(3,5- dimethoxyphenyl)-4-oxo- 4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₉H₁₆D₃NO₇S 408.44 2045

2-amino-5-(2-bromophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-dphenylmethanesulfonate-d2 C₁₇H₁₁D₃BrNO₅S 427.28 2045(R)

(R)-2-amino-5-(2- bromophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₁D₃BrNO₅S 427.28 2045(S)

(S)-2-amino-5-(2- bromophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₁D₃BrNO₅S 427.28 2046

2-amino-5-(3-bromophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-dphenylmethanesulfonate-d2 C₁₇H₁₁D₃BrNO₅S 427.28 2046(R)

(R)-2-amino-5-(3- bromophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₁D₃BrNO₅S 427.28 2046(S)

(S)-2-amino-5-(3- bromophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₁D₃BrNO₅S 427.28 2047

2-amino-5-(4-bromophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-dphenylmethanesulfonate-d2 C₁₇H₁₁D₃BrNO₅S 427.28 2047(R)

(R)-2-amino-5-(4- bromophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₁D₃BrNO₅S 427.28 2047(S)

(S)-2-amino-5-(4- bromophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₁D₃BrNO₅S 427.28 2048

2-amino-5-(2-chloro-3- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃ClFNO₅S 400.82 2048(R)

(R)-2-amino-5-(2-chloro-3- fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₇H₁₀D₃ClFNO₅S 400.822048(S)

(S)-2-amino-5-(2-chloro-3- fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₇H₁₀D₃ClFNO₅S 400.822049

2-amino-5-(2-chloro-4- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃ClFNO₅S 400.82 2049(R)

(R)-2-amino-5-(2-chloro-4- fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₇H₁₀D₃ClFNO₅S 400.822049(S)

(S)-2-amino-5-(2-chloro-4- fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₇H₁₀D₃ClFNO₅S 400.822050

2-amino-5-(2-chloro-5- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃ClFNO₅S 400.82 2050(R)

(R)-2-amino-5-(2-chloro-5- fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₇H₁₀D₃ClFNO₅S 400.822050(S)

(S)-2-amino-5-(2-chloro-5- fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₇H₁₀D₃ClFNO₅S 400.822051

2-amino-5-(2-chloro-6- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃ClFNO₅S 400.82 2051(R)

(R)-2-amino-5-(2-chloro-6- fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₇H₁₀D₃ClFNO₅S 400.822051(S)

(S)-2-amino-5-(2-chloro-6- fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₇H₁₀D₃ClFNO₅S 400.822052

2-amino-5-(3-chloro-2- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃ClFNO₅S 400.82 2052(R)

(R)-2-amino-5-(3-chloro-2- fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₇H₁₀D₃ClFNO₅S 400.822052(S)

(S)-2-amino-5-(3-chloro-2- fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₇H₁₀D₃ClFNO₅S 400.822053

2-amino-5-(3-chloro-4- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃ClFNO₅S 400.82 2053(R)

(R)-2-amino-5-(3-chloro-4- fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₇H₁₀D₃ClFNO₅S 400.822053(S)

(S)-2-amino-5-(3-chloro-4- fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₇H₁₀D₃ClFNO₅S 400.822054

2-amino-5-(3-chloro-5- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃ClFNO₅S 400.82 2054(R)

(R)-2-amino-5-(3-chloro-5- fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₇H₁₀D₃ClFNO₅S 400.822054(S)

(S)-2-amino-5-(3-chloro-5- fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₇H₁₀D₃ClFNO₅S 400.822055

2-amino-5-(5-chloro-2- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃ClFNO₅S 400.82 2055(R)

(R)-2-amino-5-(5-chloro-2- fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₇H₁₀D₃ClFNO₅S 400.822055(S)

(S)-2-amino-5-(5-chloro-2- fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₇H₁₀D₃ClFNO₅S 400.822056

2-amino-5-(4-chloro-2- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃ClFNO₅S 400.82 2056(R)

(R)-2-amino-5-(4-chloro-2- fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₇H₁₀D₃ClFNO₅S 400.822056(S)

(S)-2-amino-5-(4-chloro-2- fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₇H₁₀D₃ClFNO₅S 400.822057

2-amino-5-(4-chloro-3- fluorophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₀D₃ClFNO₅S 400.82 2057(R)

(R)-2-amino-5-(4-chloro-3- fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₇H₁₀D₃ClFNO₅S 400.822057(S)

(S)-2-amino-5-(4-chloro-3- fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₇H₁₀D₃ClFNO₅S 400.822058

2-amino-4-oxo-5-(o-tolyl)- 4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₈H₁₄D₃NO₅S 362.41 2058(R)

(R)-2-amino-4-oxo-5-(o- tolyl)-4,5-dihydrofuran-3-yl- 5-dphenylmethanesulfonate-d2 C₁₈H₁₄D₃NO₅S 362.41 2058(S)

(S)-2-amino-4-oxo-5-(o- tolyl)-4,5-dihydrofuran-3-yl- 5-dphenylmethanesulfonate-d2 C₁₈H₁₄D₃NO₅S 362.41 2059

2-amino-4-oxo-5-(m-tolyl)- 4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₈H₁₄D₃NO₅S 362.41 2059(R)

(R)-2-amino-4-oxo-5-(m- tolyl)-4,5-dihydrofuran-3-yl- 5-dphenylmethanesulfonate-d2 C₁₈H₁₄D₃NO₅S 362.41 2059(S)

(S)-2-amino-4-oxo-5-(m- tolyl)-4,5-dihydrofuran-3-yl- 5-dphenylmethanesulfonate-d2 C₁₈H₁₄D₃NO₅S 362.41 2060

2-amino-4-oxo-5-(p-tolyl)- 4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₈H₁₄D₃NO₅S 362.41 2060(R)

(R)-2-amino-4-oxo-5-(p- tolyl)-4,5-dihydrofuran-3-yl- 5-dphenylmethanesulfonate-d2 C₁₈H₁₄D₃NO₅S 362.41 2060(S)

(S)-2-amino-4-oxo-5-(p- tolyl)-4,5-dihydrofuran-3-yl- 5-dphenylmethanesulfonate-d2 C₁₈H₁₄D₃NO₅S 362.41 2061

2-amino-5-(3-cyanophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-dphenylmethanesulfonate-d2 C₁₈H₁₁D₃N₂O₅S 373.40 2061(R)

(R)-2-amino-5-(3- cyanophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₈H₁₁D₃N₂O₅S 373.40 2061(S)

(S)-2-amino-5-(3- cyanophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₈H₁₁D₃N₂O₅S 373.40 2062

2-amino-5-(4-cyanophenyl)- 4-oxo-4,5-dihydrofuran-3-yl- 5-dphenylmethanesulfonate-d2 C₁₈H₁₁D₃N₂O₅S 373.40 2062(R)

(R)-2-amino-5-(4- cyanophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₈H₁₁D₃N₂O₅S 373.40 2062(S)

(S)-2-amino-5-(4- cyanophenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₈H₁₁D₃N₂O₅S 373.40 2063

2-amino-4-oxo-5-phenyl-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₂D₃NO₅S 348.39 2063(R)

(R)-2-amino-4-oxo-5-phenyl- 4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₂D₃NO₅S 348.39 2063(S)

(S)-2-amino-4-oxo-5-phenyl- 4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₇H₁₂D₃NO₅S 348.39 2064

2-amino-4-oxo-5-(2- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₈H₁₁D₃F₃NO₅S 416.39 2064(R)

(R)-2-amino-4-oxo-5-(2- (trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₈H₁₁D₃F₃NO₅S 416.392064(S)

(S)-2-amino-4-oxo-5-(2- (trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₈H₁₁D₃F₃NO₅S 416.392065

2-amino-4-oxo-5-(3- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₈H₁₁D₃F₃NO₅S 416.39 2065(R)

(R)-2-amino-4-oxo-5-(3- (trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₈H₁₁D₃F₃NO₅S 416.392065(S)

(S)-2-amino-4-oxo-5-(3- (trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₈H₁₁D₃F₃NO₅S 416.392066

2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₈H₁₁D₃F₃NO₅S 416.39 2066(R)

(R)-2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₈H₁₁D₃F₃NO₅S 416.392066(S)

(S)-2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₈H₁₁D₃F₃NO₅S 416.392067

2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl-5-d(4- fluorophenyl) methanesulfonate-d2 C₁₈H₁₀D₃F₄NO₅S 434.38 2067(R)

(R)-2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d (4- fluorophenyl) methanesulfonate-d2C₁₈H₁₀D₃F₄NO₅S 434.38 2067(S)

(S)-2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d (4- fluorophenyl) methanesulfonate-d2C₁₈H₁₀D₃F₄NO₅S 434.38 2068

methyl 4-(5-amino-4-((((4- fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3- dihydrofuran-2-yl-2- d)benzoateC₁₉H₁₃D₃FNO₇S 424.41 2068(R)

methyl (R)-4-(5-amino-4- ((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3- dihydrofuran-2-yl-2- d)benzoateC₁₉H₁₃D₃FNO₇S 424.41 2068(S)

methyl (S)-4-(5-amino-4- ((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3- dihydrofuran-2-yl-2- d)benzoateC₁₉H₁₃D₃FNO₇S 424.41 2069

ethyl 4-(5-amino-4-((((4- fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3- dihydrofuran-2-yl-2- d)benzoateC₂₀H₁₅D₃FNO₇S 438.44 2069(R)

ethyl (R)-4-(5-amino-4-((((4- fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3- dihydrofuran-2-yl-2- d)benzoateC₂₀H₁₅D₃FNO₇S 438.44 2069(S)

ethyl (S)-4-(5-amino-4-((((4- fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3- dihydrofuran-2-yl-2- d)benzoateC₂₀H₁₅D₃FNO₇S 438.44 2070

4-(5-amino-4-((((4- fluorophenyl)methyl- d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2- d)benzoic acid-d C₁₈H₁₀D₄FNO₇S 411.39 2070(R)

(R)-4-(5-amino-4-((((4- fluorophenyl)methyl- d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2- d)benzoic acid-d C₁₈H₁₀D₄FNO₇S 411.39 2070(S)

(S)-4-(5-amino-4-((((4- fluorophenyl)methyl- d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2- d)benzoic acid-d C₁₈H₁₀D₄FNO₇S 411.39 2071

methyl 4-(5-amino-4-((((4- fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3- dihydrofuran-2-yl-2-d)-2- fluorobenzoateC₁₉H₁₂D₃F₂NO₇S 442.40 2071(R)

methyl (R)-4-(5-amino-4- ((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3- dihydrofuran-2-yl-2-d)-2- fluorobenzoateC₁₉H₁₂D₃F₂NO₇S 442.40 2071(S)

methyl (S)-4-(5-amino-4- ((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3- dihydrofuran-2-yl-2-d)-2- fluorobenzoateC₁₉H₁₂D₃F₂NO₇S 442.40 2072

2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5 dihydrofuran-3-yl-5-d(phenyl- d5)methanesulfonate-d2 C₁₈H₆D₈F₃NO₅S 421.42 2072(R)

(R)-2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5dihydrofuran-3-yl-5-d (phenyl- d5)methanesulfonate-d2 C₁₈H₆D₈F₃NO₅S421.42 2072(S)

(S)-2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d (phenyl- d5)methanesulfonate-d2 C₁₈H₆D₈F₃NO₅S421.42 2073

methyl 4-(5-amino-3-oxo-4- ((((phenyl-d5)methyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2- d)benzoate C₁₉H₉D₈NO₇S 411.45 2073(R)

methyl (R)-4-(5-amino-3- oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2- d)benzoate C₁₉H₉D₈NO₇S 411.452073(S)

methyl (S)-4-(5-amino-3- oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2- d)benzoate C₁₉H₉D₈NO₇S 411.452074

ethyl 4-(5-amino-3-oxo-4- ((((phenyl-d5)methyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2- d)benzoate C₂₀H₁₁D₈NO₇S 425.48 2074(R)

ethyl (R)-4-(5-amino-3-oxo- 4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2- d)benzoate C₂₀H₁₁D₈NO₇S425.48 2074(S)

ethyl (S)-4-(5-amino-3-oxo- 4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2- d)benzoate C₂₀H₁₁D₈NO₇S425.48 2075

4-(5-amino-3-oxo-4- ((((phenyl-d5)methyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2- d)benzoic acid-d C₁₈H₆D₉NO₇S 398.43 2075(R)

(R)-4-(5-amino-3-oxo-4- ((((phenyl-d5)methyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2- d)benzoic acid-d C₁₈H₆D₉NO₇S 398.43 2075(S)

(S)-4-(5-amino-3-oxo-4- ((((phenyl-d5)methyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2- d)benzoic acid-d C₁₈H₆D₉NO₇S 398.43 2076

methyl 4-(5-amino-3-oxo-4- ((((phenyl-d5)methyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)-2- fluorobenzoate C₁₉H₈D₈FNO₇S 429.44 2076(R)

methyl (R)-4-(5-amino-3- oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2-d)-2- fluorobenzoateC₁₉H₈D₈FNO₇S 429.44 2076(S)

methyl (S)-4-(5-amino-3- oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3- dihydrofuran-2-yl-2-d)-2- fluorobenzoateC₁₉H₈D₈FNO₇S 429.44 2077

2-amino-5- (benzo[d][1,3]dioxol-5-yl)-4- oxo-4,5-dihydrofuran-3-yl-5- dphenylmethanesulfonate- d2 C₁₈H₁₂D₃NO₇S 392.40 2077(R)

(R)-2-amino-5- (benzo[d][1,3]dioxol-5-yl)-4-oxo-4,5-dihydrofuran-3-yl-5- d phenylmethanesulfonate- d2 C₁₈H₁₂D₃NO₇S392.40 2077(S)

(S)-2-amino-5- (benzo[d][1,3]dioxol-5-yl)-4-oxo-4,5-dihydrofuran-3-yl-5- d phenylmethanesulfonate- d2 C₁₈H₁₂D₃NO₇S392.40 2078

2-amino-5-(2,2- difluorobenzo[d][1,3]dioxol- 5-yl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₈H₁₀D₃F₂NO₇S 428.382078(R)

(R)-2-amino-5-(2,2- difluorobenzo[d][1,3]dioxol- 5-yl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₈H₁₀D₃F₂NO₇S 428.382078(S)

(S)-2-amino-5-(2,2- difluorobenzo[d][1,3]dioxol- 5-yl)-4-oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₈H₁₀D₃F₂NO₇S 428.382079

methyl2-(4-(5-amino-3-oxo- 4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2- d)phenyl)acetate-d2 C₂₀H₁₄D₅NO₇S 422.46 2079(R)

methyl (R)-2-(4-(5-amino-3- oxo-4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2- d)phenyl)acetate-d2 C₂₀H₁₄D₅NO₇S 422.46 2079(S)

methyl (S)-2-(4-(5-amino-3- oxo-4-(((phenylmethyl- d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2- d)phenyl)acetate-d2 C₂₀H₁₄D₅NO₇S 422.46 2080

2-amino-5-(4-(carbamoyl- d2)phenyl)-4-oxo-4,5- dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2 C₁₈H₁₁D₅N₂O₆S 393.42 2080(R)

(R)-2-amino-5-(4- (carbamoyl-d2)phenyl)-4- oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate- d2 C₁₈H₁₁D₅N₂O₆S 393.42 2080(S)

(S)-2-amino-5-(4- (carbamoyl-d2)phenyl)-4- oxo-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate- d2 C₁₈H₁₁D₅N₂O₆S 393.42 2081

2-amino-4-oxo-5-(6- (trifluoromethyl)pyridin-3-yl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₇H₁₀D₃F₃N₂O₅S417.37 2081(R)

(R)-2-amino-4-oxo-5-(6- (trifluoromethyl)pyridin-3-yl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₇H₁₀D₃F₃N₂O₅S417.37 2081(S)

(S)-2-amino-4-oxo-5-(6- (trifluoromethyl)pyridin-3-yl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₇H₁₀D₃F₃N₂O₅S417.37 2082

2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl-5-d(4- chlorophenyl)methane- sulfonate-d2 C₁₈H₁₀D₃ClF₃NO₅S 450.83 2082(R)

(R)-2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d (4- chlorophenyl)methane- sulfonate-d2C₁₈H₁₀D₃ClF₃NO₅S 450.83 2082(S)

(S)-2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d (4- chlorophenyl)methane- sulfonate-d2C₁₈H₁₀D₃ClF₃NO₅S 450.83 2083

2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-yl-5-d(4- (trifluoromethyl)phenyl) methanesulfonate-d2 C₁₉H₁₀D₃F₆NO₅S 484.382083(R)

(R)-2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d (4- (trifluoromethyl)phenyl) methanesulfonate-d2C₁₉H₁₀D₃F₆NO₅S 484.38 2084

2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5- dihydrofuran-3-ylphenylmethanesulfonate C₁₈H₁₂D₂F₃NO₅S 415.38 2085

2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₈H₉D₅F₃NO₅S 418.402085(R)

(R)-2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₈H₉D₅F₃NO₅S 418.402085(S)

(S)-2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₈H₉D₅F₃NO₅S 418.402086

2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl(phenyl- d5)methanesulfonate C₁₈H₇D₇F₃NO₅S 420.41 2087

2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d (phenyl- d5)methanesulfonate-d2 C₁₈H₄D₁₀F₃NO₅S423.43 2087(R)

(R)-2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d (phenyl- d5)methanesulfonate-d2 C₁₈H₄D₁₀F₃NO₅S423.43 2087(S)

(S)-2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d (phenyl- d5)methanesulfonate-d2 C₁₈H₄D₁₀F₃NO₅S423.43 2088

2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5-dihydrofuran-3-yl phenylmethanesulfonate C₁₈H₈D₆F₃NO₅S 419.40 2089

2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₈H₇D₇F₃NO₅S 420.412089(R)

(R)-2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₈H₇D₇F₃NO₅S 420.412089(S)

(S)-2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₈H₇D₇F₃NO₅S 420.412090

2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₈H₅D₉F₃NO₅S 422.422090(R)

(R)-2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₈H₅D₉F₃NO₅S 422.422090(S)

(S)-2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2 C₁₈H₅D₉F₃NO₅S 422.422091

2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5-dihydrofuran-3-yl(phenyl- d5)methanesulfonate C₁₈H₃D₁₁F₃NO₅S 424.43 2092

2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d (phenyl- d5)methanesulfonate-d2 C₁₈H₂D₁₂F₃NO₅S425.44 2092(R)

(R)-2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d (phenyl- d5)methanesulfonate-d2 C₁₈H₂D₁₂F₃NO₅S425.44 2092(S)

(S)-2-amino-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d (phenyl- d5)methanesulfonate-d2 C₁₈H₂D₁₂F₃NO₅S425.44 2093

2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d (phenyl- d5)methanesulfonate-d2 C₁₈D₁₄F₃NO₅S427.45 2093(R)

(R)-2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d (phenyl- d5)methanesulfonate-d2 C₁₈D₁₄F₃NO₅S427.45 2093(S)

(S)-2-(amino-d2)-4-oxo-5-(4- (trifluoromethyl)phenyl- 2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d (phenyl- d5)methanesulfonate-d2 C₁₈D₁₄F₃NO₅S427.45

Synthesis of Specific #2000 Series of Compounds Compound [2001]:2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl methanesulfonate

A sample of 1.07 mmoles roc-1001 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2001-d₄ is performed to yield2001(S) and 2001(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound [2002]:2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-ylethanesulfonate

A sample of 1.07 mmoles roc-1002 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2002-d₃ is performed to yield2002(S) and 2002(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2003}: 2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-ylpropone-1-sulfonate

A sample of 1.07 mmoles rac-1003 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2003-d₃ is performed to yield2003(S) and 2003(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2004}: 2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-ylpropone-2-sulfonate

A sample of 1.07 mmoles rac-1004 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2004-d₂ is performed to yield2004(S) and 2004(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2005}: 2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-ylbutane-1-sulfonate

A sample of 1.07 mmoles rac-1005 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2005-d₃ is performed to yield2005(S) and 2005(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2006}: 2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl2-methylpropone-1-sulfonate

A sample of 1.07 mmoles rac-1006 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2006-d₃ is performed to yield2006(S) and 2006(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2007}: 2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-ylbenzenesulfonate-d5

A sample of 1.07 mmoles rac-1007 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2007-d is performed to yield2007(S) and 2007(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2008}: 2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1008 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2008-d₃ is performed to yield2008(S) and 2008(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2009}: 2-amino-5-(2-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1009 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2009-d₃ is performed to yield2009(S) and 2009(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2010}: 2-amino-5-(3-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1010 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2010-d₃ is performed to yield2010(S) and 2010(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2011}:2-amino-5-(2,3-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1011 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2011-d₃ is performed to yield2011(S) and 2011(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2012}:2-amino-5-(2,4-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1012 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2012-d₃ is performed to yield2012(S) and 2012(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2013}:2-amino-5-(2,5-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1013 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2013-d₃ is performed to yield2013(S) and 2013(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2014}:2-amino-5-(3,4-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1014 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2014-d₃ is performed to yield2014(S) and 2014(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2015}:2-amino-5-(3,5-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1015 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2015-d₃ is performed to yield2015(S) and 2015(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2016}: methyl3-(5-amino-4-((benzylsulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl)benzoate

A sample of 1.07 mmoles rac-1016 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2016-d₃ is performed to yield2016(S) and 2016(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2017}: methyl4-(5-amino-4-((benzylsulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl)benzoate

A sample of 1.07 mmoles rac-1017 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2017-d₃ is performed to yield2017(S) and 2017(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2018}: methyl4-(5-amino-4-((benzylsulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl)-2-fluorobenzoate

A sample of 1.07 mmoles rac-1018 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2018-d₃ is performed to yield2018(S) and 2018(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2019}: ethyl4-(5-amino-4-((benzylsulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl)benzoate

A sample of 1.07 mmoles rac-1019 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2019-d₃ is performed to yield2019(S) and 2019(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2020}: 5-(4-acetylphenyl)-2-amino-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1020 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2020-d₃ is performed to yield2020(S) and 2020(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2021}:2-amino-5-(4-carbamoylphenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1021 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2021-d₃ is performed to yield2021(S) and 2021(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2022}:4-(5-amino-4((benzylsulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl)benzoicacid

A sample of 1.07 mmoles rac-1022 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is neutralized with CD₃CO₂D to a pH=5.0, andconcentrated under reduced pressure. Preparative chiral HPLC separationof enantiomers of 2022-d₃ is performed to yield 2022(S) and 2022(R).Fractions are collected at −78° C. (dry-ice cooling) to preventracemization. Evaporation under reduced pressure affords the product aswhite solids.

Compound {2023}: Sodium4-(5-amino-4-((benzylsulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl)benzoate

A sample of 1.07 mmoles rac-1022 is stirring in 10 mL of THF in thepresence of 4.69 mmoles Na₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2023-d₃ is performed to yield2023(S) and 2023(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2024}: Potassium4-(5-amino-4-((benzylsulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl)benzoate

A sample of 1.07 mmoles rac-1022 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2024-d₃ is performed to yield2024(S) and 2024(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2025}: potassium4-(5-amino-4-((benzylsulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl)benzoate

A sample of 1.07 mmoles rac-1022 is stirring in 10 mL of THF in thepresence of 4.69 mmoles MgCO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2025-d₃ is performed to yield2025(S) and 2025(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2026}: Calcium4-(5-amino-4-((benzylsulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl)benzoate

A sample of 1.07 mmoles rac-1022 is stirring in 10 mL of THF in thepresence of 4.69 mmoles CaCO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2026-d₃ is performed to yield2026(S) and 2026(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2027}: 2-amino-5-(2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1027 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2027-d₃ is performed to yield2027(S) and 2027(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2028}: 2-amino-5-(3-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1028 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2028-d₃ is performed to yield2028(S) and 2028(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2029}: 2-amino-5-(4-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1029 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2029-d₃ is performed to yield2029(S) and 2029(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2030}:2-amino-5-(2,3-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1030 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2030-d₃ is performed to yield2030(S) and 2030(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2031}:2-amino-5-(2,4-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1031 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2031-d₃ is performed to yield2031(S) and 2031(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2032}:2-amino-5-(2,5-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1032 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2032-d₃ is performed to yield2032(S) and 2032(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2033}:2-amino-5-(2,6-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1033 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2033-d₃ is performed to yield2033(S) and 2033(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2034}:2-amino-5-(3,4-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1034 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2034-d₃ is performed to yield2034(S) and 2034(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2035}:2-amino-5-(3,5-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1035 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2035-d₃ is performed to yield2035(S) and 2035(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2036}: 2-amino-5-(2-methoxyphenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1036 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2036-d₃ is performed to yield2036(S) and 2036(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2037}: 2-amino-5-(3-methoxyphenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1037 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2037-d₃ is performed to yield2037(S) and 2037(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2038}: 2-amino-5-(4-methoxyphenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1038 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2038-d₃ is performed to yield2038(S) and 2038(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2039}:2-amino-5-(2,3-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1039 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2039-d₃ is performed to yield2039(S) and 2039(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2040}:2-amino-5-(2,4-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1040 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2040-d₃ is performed to yield2040(S) and 2040(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2041}:2-amino-5-(2,5-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1041 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2041-d₃ is performed to yield2041(S) and 2041(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2042}:2-amino-5-(2,6-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1042 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2042-d₃ is performed to yield2042(S) and 2042(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2043}:2-amino-5-(3,4-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1043 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2043-d₃ is performed to yield2043(S) and 2043(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2044}:2-amino-5-(3,5-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1044 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2044-d₃ is performed to yield2044(S) and 2044(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2045}: 2-amino-5-(2-bromophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1045 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2045-d₃ is performed to yield2045(S) and 2045(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2046}: 2-amino-5-(3-bromophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1046 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2046-d₃ is performed to yield2046(S) and 2046(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2047}: 2-amino-5-(4-bromophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1047 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2047-d₃ is performed to yield2047(S) and 2047(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2048}:2-amino-5-(2-chloro-3-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1048 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2048-d₃ is performed to yield2048(S) and 2048(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2049}:2-amino-5-(2-chloro-4-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1049 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2049-d₃ is performed to yield2049(S) and 2049(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound [2050]:2-amino-5-(2-chloro-5-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles roc-1050 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2050-d₃ is performed to yield2050(S) and 2050(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2051}:2-amino-5-(2-chloro-6-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1051 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2051-d₃ is performed to yield2051(S) and 2051(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2052}:2-amino-5-(3-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1052 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2052-d₃ is performed to yield2052(S) and 2052(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2053}:2-amino-5-(3-chloro-4-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1053 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K2CO3 and 2 mL D20 at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2053-d₃ is performed to yield2053(S) and 2053(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2054}:2-amino-5-(3-chloro-5-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1054 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2054-d₃ is performed to yield2054(S) and 2054(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2055}:2-amino-5-(5-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1055 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2055-d₃ is performed to yield2055(S) and 2055(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2056}:2-amino-5-(4-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1056 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2056-d₃ is performed to yield2056(S) and 2056(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2057}:2-amino-5-(4-chloro-3-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1057 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2057-d₃ is performed to yield2057(S) and 2057(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2058}: 2-amino-4-oxo-5-(o-tolyl)-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1058 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2058-d₃ is performed to yield2058(S) and 2058(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2059}: 2-amino-4-oxo-5-(m-tolyl)-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1059 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2059-d₃ is performed to yield2059(S) and 2059(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2060}: 2-amino-4-oxo-5-(p-tolyl)-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1060 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2060-d₃ is performed to yield2060(S) and 2060(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2061}: 2-amino-5-(3-cyanophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1061 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2061-d₃ is performed to yield2061(S) and 2061(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2062}: 2-amino-5-(4-cyanophenyl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1062 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2062-d₃ is performed to yield2062(S) and 2062(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2063}: 2-amino-4-oxo-5-phenyl-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1063 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2063-d₃ is performed to yield2063(S) and 2063(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2064}:2-amino-4-oxo-5-(2-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1064 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2064-d₃ is performed to yield2064(S) and 2064(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2065}:2-amino-4-oxo-5-(3-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1065 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2065-d₃ is performed to yield2065(S) and 2065(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2066}:2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of rac-1 (440 mg, 1.07 mmol) was stirred in THF (10 mL) in thepresence of K₂CO₃ (645 mg, 4.69 mmol; 4.4 eq.) and D₂O (1.77 g, 88.5mmol; 82.6 eq.) at room temperature. The reaction progress was monitoredby LCMS and Mass analysis. After 9 days a sample was taken andconcentrated under reduced pressure to give 96-100% pure (LCMS, UV 215and 254 nm respectively) racemic 1-d₃ (38.9 mg) according to ¹H-NMRanalysis. LCMS analysis of the NMR sample (in dmso-d6) showeddeuterium/hydrogen exchange after standing at room temperature to give1-d₂ as major component. LCMS analysis using another column andequipment also showed that deuterium loss took place in dmso-d6. A freshsample was prepared and analyzed directly after dissolving in THF,instead of dmso-d6, to demonstrate the presence of 1-d₃ as majorcomponent. Calcd. for C₁₈H₁₁D₃F₃NO₅S M: 416.39

LCMS purity: 84.6% (at 216 nm) and 89.8% (at 264 nm) MS (ES⁺): m/z: 417[M+1] MS (ES⁻): m/z: 415 [M−1]

¹H-NMR (rac-1-d₃ in dmso-d6): 7.37 (m, 3H); 7.51 (m, 4H); 7.82 (m, 2H);8.80 (br s, 2H)

¹⁹F-NMR (rac-1-d₃ in dmso-d6): −61.10 ppm

Preparative chiral HPLC separation of enantiomers of 1-d₃ (ca. 380 mg in8 mL THF) was performed in two batches using a preparative Chiralpak IAcolumn (250×20 mm). Fractions were collected at −78° C. (dry-ice boxcooling) to prevent racemization. Evaporation under reduced pressureafforded the first batch of 36.2 mg enantiomer 1 and 32.5 mg enantiomer2 as white solids. The second batch gave 50.1 mg enantiomer 1 and 51.9mg enantiomer 2. All enantiomers were >99% chemically pure (LCMS). Theee of the separated enantiomers varied from 96.4 to 99.8% ee. The firsteluting enantiomer 1 of 1-d₃ had a (−) optical rotation, whereas thesecond eluting enantiomer 2 of 1-d₃ had a (+) optical rotation accordingto additional chiral laser polarimeter detection in the chiral HPLC.

Calcd. for C₁₈H₁₁D₃F₃NO₅S M: 416.39 found MS (ES⁺): m/z: 417 [M+1]

(−)-1-d₃ Enantiomer 1

36.2 mg, 99.6% ee; Purity: 99.6% (at 216 nm) and 99.5% (at 264 nm) MS(ES⁺): m/z: 417 [M+1] MS (ES⁻): m/z: 415 [M−1]

(+)-1-d₃ Enantiomer 2

32.5 mg, 97.5% ee; Purity: 99.5% (at 216 nm) and 99.5% (at 264 nm) MS(ES⁺): m/z: 417 [M+1] MS (ES⁻): m/z: 415 [M−1]

Compound {2067}:2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl(4-fluorophenyl)methanesulfonate

A sample of 1.07 mmoles rac-1067 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2067-d₃ is performed to yield2067(S) and 2067(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2068}: methyl4-(5-amino-4-(((4-fluorobenzyl)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl)benzoate

A sample of 1.07 mmoles rac-1068 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2068-d₃ is performed to yield2068(S) and 2068(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2069}: ethyl4-(5-amino-4-(((4-fluorobenzyl)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl)benzoate

A sample of 1.07 mmoles rac-1069 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2069-d₄ is performed to yield2069(S) and 2069(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2070}:4-(5-amino-4-(((4-fluorobenzyl)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl)benzoicacid

A sample of 1.07 mmoles rac-1070 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is neutralized with CD₃CO₂D to pH=5.0, andconcentrated under reduced pressure. Preparative chiral HPLC separationof enantiomers of 2070-d₃ is performed to yield 2070(S) and 2070(R).Fractions are collected at −78° C. (dry-ice cooling) to preventracemization. Evaporation under reduced pressure affords the product aswhite solids.

Compound {2071}: methyl4-(5-amino-4-(((4-fluorobenzyl)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl)-2-fluorobenzoate

A sample of 1.07 mmoles rac-1071 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2071-d₈ is performed to yield2071(S) and 2071(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2072}:2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl(phenyl-d5)methanesulfonate

A sample of 1.07 mmoles rac-1072 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2072-d₈ is performed to yield2072(S) and 2072(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2073}: methyl4-(5-amino-3-oxo-4-((((phenyl-d5)methyl)sulfonyl)oxy)-2,3-dihydrofuran-2-yl)benzoate

A sample of 1.07 mmoles rac-1073 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2073-d₈ is performed to yield2073(S) and 2073(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2074}: ethyl4-(5-amino-3-oxo-4-((((phenyl-d5)methyl)sulfonyl)oxy)-2,3-dihydrofuran-2-yl)benzoate

A sample of 1.07 mmoles rac-1074 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2074-d₈ is performed to yield2074(S) and 2074(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2075}:4-(5-amino-3-oxo-4-((((phenyl-d5)methyl)sulfonyl)oxy)-2,3-dihydrofuran-2-yl)benzoicacid

A sample of 1.07 mmoles rac-1075 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2075-d₈ is performed to yield2075(S) and 2075(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2076}: methyl4-(5-amino-3-oxo-4-((((phenyl-d5)methyl)sulfonyl)oxy)-2,3-dihydrofuran-2-yl)-2-fluorobenzoate

A sample of 1.07 mmoles rac-1076 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2076-d₈ is performed to yield2076(S) and 2076(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2077}:2-amino-5-(benzo[d][1,3]dioxol-5-yl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1077 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2077-d₃ is performed to yield2077(S) and 2077(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2078}:2-amino-5-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-4-oxo-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1078 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2078-d₃ is performed to yield2078(S) and 2078(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2079}: methyl2-(4-(5-amino-4-((benzylsulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl)phenyl)acetate

A sample of 1.07 mmoles rac-1079 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2079-d₅ is performed to yield2079(S) and 2079(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2080}:2-amino-5-(4-(carbamoyl-d2)phenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2

A sample of 1.07 mmoles rac-1021 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2080-d₅ is performed to yield2080(S) and 2080(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2081}:2-amino-4-oxo-5-(6-(trifluoromethyl)pyridin-3-yl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2

A sample of 1.07 mmoles rac-1081 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2081-d₃ is performed to yield2081(S) and 2081(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2082}:2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d(4-chlorophenyl)methanesulfonate-d2

A sample of 1.07 mmoles rac-1082 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2082-d₃ is performed to yield2082(S) and 2082(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2083}:2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d(4-(trifluoromethyl)phenyl)methanesulfonate-d2

A sample of 1.07 mmoles rac-1083 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2083-d₃ is performed to yield2083(S) and 2083(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2084}:2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1066 is stirring in 10 mL of CF₃CO₂D atroom. After 1 day the reaction is frozen, and concentrated under reducedpressure.

Compound {2085}:2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2

A sample of 1.07 mmoles rac-2084 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2085-d₅ is performed to yield2085(S) and 2085(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2086}:2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl(phenyl-d5)methanesulfonate

A sample of 1.07 mmoles rac-1072 is stirring in 10 mL of CF₃CO₂D at roomtemperature. After 1 day the reaction is frozen, and concentrated underreduced pressure.

Compound {2087}:2-(amino-d2)-4-oxo-5-(4-trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2

A sample of 1.07 mmoles rac-2086 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2087-d₁₀ is performed to yield2087(S) and 2087(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2088}:2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-ylphenylmethanesulfonate

A sample of 1.07 mmoles rac-1084 is stirring in 10 mL of CF₃CO₂D at roomtemperature. After 1 day the reaction is frozen, and concentrated underreduced pressure.

Compound [2089]:2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2

A sample of 1.07 mmoles roc-1084 is stirring in 10 mL of THF in thepresence of CF₃CO₂D [[4.69 mmoles K₂CO₃ and 2 mL D₂O]] at roomtemperature. After 1 day the reaction is frozen, and concentrated underreduced pressure. The sample is resuspending in THF, and is stirring in10 mL of THF in the presence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at roomtemperature. After 9 days the reaction is concentrated under reducedpressure. Preparative chiral HPLC separation of enantiomers of 2089-d₇is performed to yield 2089(S) and 2089(R). Fractions are collected at−78° C. (dry-ice cooling) to prevent racemization. Evaporation underreduced pressure affords the product as white solids.

Compound {2090}:2-d2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2

A sample of 1.07 mmoles roc-1084 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2090-d₇ is performed to yield2090(S) and 2090(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2091}:2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl(phenyl-d5)methanesulfonate

A sample of 1.07 mmoles rac-1085 is stirring in 10 mL of CF₃CO₂D at roomtemperature. After 1 day the reaction is frozen, and concentrated underreduced pressure.

Compound {2092}:2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d(phenyl-d5)methanesulfonate-d2

A sample of 1.07 mmoles rac-1085 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2092-d₁₂ is performed to yield2092(S) and 2092(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Compound {2093}:2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d(phenyl-d5)methanesulfonate-d2

A sample of 1.07 mmoles rac-2091 is stirring in 10 mL of THF in thepresence of 4.69 mmoles K₂CO₃ and 2 mL D₂O at room temperature. After 9days the reaction is concentrated under reduced pressure. Preparativechiral HPLC separation of enantiomers of 2093-d₁₄ is performed to yield2093(S) and 2093(R). Fractions are collected at −78° C. (dry-icecooling) to prevent racemization. Evaporation under reduced pressureaffords the product as white solids.

Example 3—Demonstrating Enhanced Metabolic Stability of ExemplaryCompounds

Exemplary compounds are typically incubated with human, dog, cat, mouse,rat, or monkey liver or intestinal microsomes under standard reactionconditions. Two samples from each reaction mixture are taken at timeintervals, such as 0, 15, 30, 45 and 60 minutes and injected onto anHPLC column to detect and quantify the absolute and/or relative levelsof the unmetabolized compound. The Clint and the half-life for eachmolecule are calculated. Reference compounds for direct comparisoninclude imipramine, propranolol, terfenadine, and verapamil.

Metabolic stability was performed by a commercial laboratory using astandard protocol. Compounds #1066, #2066, #2066(R), and #2066(S) werediluted to 1E-7 M, and incubated with human liver microsomes, or mouseliver microsomes (0.1 mg/mL), and quantified by HPLC. Control compoundswere imipramine, propranolol, terfenadine and verapamil, which behavednormally as expected. Metabolic stability, expressed as percent of theparent compound remaining, was calculated by comparing the peak area ofthe compound at the time point relative to that at time at 0, 15, 30, 45and 60 minutes. The half-life (T½) was estimated from the slope of theinitial linear range of the logarithmic curve of compound remaining (%)vs. time, assuming the first-order kinetics. The apparent intrinsicclearance (CLint, in μL/min/pmol, μL/min/mg or μL/min/Mcell) wascalculated.

FIG. 8 illustrates the activities of undeuterated, racemic, anddeuterated enantiomers of tetronimide modulator compounds against ASPHin liver microsome assays.

Example 4—Demonstrating In Vitro Biological Activity of ExemplaryCompounds

5000 MCF-7 cells were plated in appropriate media, and 0, 1.25, 2.5, 5or 10 uM of each compound was added. All experiments were performed intriplicate. After 24 hours, cell viability was measured using a standardMTT kit assay.

FIG. 9 illustrates the activities of specific compounds #1066, #2066(R),and #2066(S) against MCF-7 Cells In Vitro.

Example 5—Demonstration In Vivo Biological Activity of ExemplaryCompounds

Mice, such as strains BALB/cJ or C57BL/6NJ or NOD SCID, are divided into6 groups of 5 mice per compound, one group for untreated, one group forvehicle control, one group for undeuterated compound (for example,#1066), one group for racemic deuterated (for example, #2066), one groupfor (R) isomer deuterated compound (for example, #2066(R)), and onegroup for (S) deuterated compound (for example, #2066(S)). The selectedmouse strain is injected with a cancer cell line (such as osteosarcoma,mammary carcinoma, ovarian carcinoma, hepatocellular carcinoma,glioblastoma multiform, neuroblastoma, pancreatic adenocarcinoma, andcholangiocarcinoma cells) that is ASPH positive into the right flanksubcutaneously. Untreated animals are left untreated. Vehicle controlmice are administered Size “M” capsules containing only lactose daily.Mice in the undeuterated compound group are administered undeuteratedcompound triturated with lactose at 10 mg/kg in a Size “M” capsuledaily. Deuterated racemic compound group is administered racemicdeuterated compound triturated with lactose a 10 mg/kg in a Size “M”capsule daily. Mice in the (R) deuterated group are administered the (R)deuterated compound 10 mg/kg that has been triturated with lactose andpackaged into a Size “M” capsule daily. Mice in the (S) deuterated groupare administered the (S) deuterated compound 10 mg/kg that has beentriturated with lactose and packaged into a Size “M” capsule daily. Thesize of the tumor is being measured daily, either until death or untilday 30 when all animals are sacrificed. Tumors are being excised uponanimal death or sacrifice, all tumors are weighed, and metastasis arebeing counted. At the time of death or sacrifice, animal blood iscollected, and blood or serum cholesterol, complement activity, bloodcoagulation parameters (INR, aPTT) and liver enzymes (ALT, AST and GGT)are quantified.

Statement Regarding Preferred Aspects are Meant to be Illustrative andnot Limiting as to the Scope of the Invention

While the preferred aspects of the invention have been illustrated anddescribed in detail, it will be appreciated by those skilled in the artthat that various changes can be made therein without departing from thespirit and scope of the invention. Accordingly, the particulararrangements disclosed are meant to be illustrative only and notlimiting as to the scope of the invention, which is to be given the fullbreadth of the appended claims and any equivalent thereof.

REFERENCES

Statement Regarding Incorporation by Reference of Journal Articles andPatent Documents

All references, as journal articles or patent documents (publishedapplications or issued patents), cited herein, are incorporated byreference in their entirety, as if written herein.

Journal Articles

-   1. AIHARA, A., C. K. HUANG, M. J. OLSEN, Q. LIN, W. CHUNG, Q    TANG, X. DONG AND J. R. WANDS (2014). “A cell-surface    beta-hydroxylase is a biomarker and therapeutic target for    hepatocellular carcinoma.” Hepatology 60(4): 1302-1313.-   2. BORGAS, D. L., J. S. GAO, M. TONG AND S. M. DE LA MONTE (2015).    “Potential Role of Phosphorylation as a Regulator of    Aspartyl-(asparaginyl)-beta-hydroxylase: Relevance to Infiltrative    Spread of Human Hepatocellular Carcinoma.” Liver Cancer 4(3):    139-153.-   3. BORGAS, D. L, J. S. GAO, M. TONG, N. ROPER AND S. M. DE LA MONTE    (2015). “Regulation of Aspartyl-(Asparaginyl)-beta-Hydroxylase    Protein Expression and Function by Phosphorylation in Hepatocellular    Carcinoma Cells.” J Nat Sci 1(4).-   4. CANTARINI, M. C., S. M. DE LA MONTE, M. PANG, M. TONG, A.    D'ERRICO, F. TREVISANI AND J. R. WANDS (2006). “Aspartyl-asparagyl    beta hydroxylase over-expression in human hepatoma is linked to    activation of insulin-like growth factor and notch signaling    mechanisms.” Hepatology 44(2): 446-457.-   5. DINCHUK, J. E., R. J. FOCHT, J. A. KELLEY, N. L HENDERSON, N. I.    ZOLOTARJOVA, R. WYNN, N. T. NEFF, J. LINK, R. M. HUBER, T. C.    BURN, M. J. RUPAR, M. R. CUNNINGHAM, B. H. SELLING, J. MA, A. A.    STERN, G. F. HOLLIS, R. B. STEIN AND P. A. FRIEDMAN (2002). “Absence    of post-translational aspartyl beta-hydroxylation of epidermal    growth factor domains in mice leads to developmental defects and an    increased incidence of intestinal neoplasia.” J Biol Chem 277(15):    12970-12977.-   6. DRAKENBERG, T., P. FERNLUND, P. ROEPSTORFF AND J. STENFLO (1983).    “beta-Hydroxyaspartic acid in vitamin K-dependent protein C.” Proc    Natl Acad Sci USA 80(7): 1802-1806.-   7. EL ASMAR, Z., J. TERRAND, M. JENTY, L HOST, M. MLIH, A. ZERR, H.    JUSTINIANO, R. L. MATZ, C. BOUDIER, E. SCHOLLER, J. M. GARNIER, D.    BERTACCINI, D. THIERSE, C. SCHAEFFER, A. VAN DORSSELAER, J. HERZ, V.    BRUBAN AND P. BOUCHER (2016). “Convergent Signaling Pathways    Controlled by LRP1 (Receptor-related Protein 1) Cytoplasmic and    Extracellular Domains Limit Cellular Cholesterol Accumulation.” J    Biol Chem 291(10): 5116-5127.-   8. FURLER, R. L, D. F. NIXON, C. A. BRANTNER, A. POPRATILOFF    AND C. H. UITTENBOGAART (2018). “TGF-beta Sustains Tumor Progression    through Biochemical and Mechanical Signal Transduction.” Cancers    (Basel) 10(6).-   9. GUNDOGAN, F., G. ELWOOD, D. GRECO, L P. RUBIN, H. PINAR, R. I.    CARLSON, J. R. WANDS AND S. M. DE LA MONTE (2007). “Role of    aspartyl-(asparaginyl) beta-hydroxylase in placental implantation:    Relevance to early pregnancy loss.” Hum Pathol 38(1): 50-59.-   10. IWAGAMI, Y., S. CASULLI, K. NAGAOKA, M. KIM, R. I. CARLSON, K.    OGAWA, M. S. LEBOWITZ, S. FULLER, B. BISWAS, S. STEWART, X. DONG, H.    GHANBARI AND J. R. WANDS (2017). “Lambda phage-based vaccine induces    antitumor immunity in hepatocellular carcinoma.” Heliyon 3(9):    e00407.-   11. LAVAISSIERE, L, S. JIA, M. NISHIYAMA, S. DE LA MONTE, A. M.    STERN, J. R. WANDS AND P. A. FRIEDMAN (1996). “Overexpression of    human aspartyl(asparaginyl)beta-hydroxylase in hepatocellular    carcinoma and cholangiocarcinoma.” J Clin Invest 98(6): 1313-1323.-   12. NODA, T., M. SHIMODA, V. ORTIZ, A. E. SIRICA AND J. R. WANDS    (2012). “Immunization with aspartate-beta-hydroxylase-loaded    dendritic cells produces antitumor effects in a rat model of    intrahepatic cholangiocarcinoma.” Hepatology 55(1): 86-97.-   13. REVSKAYA, E., Z. JIANG, A. MORGENSTERN, F. BRUCHERTSEIFER, M.    SESAY, S. WALKER, S. FULLER, M. S. LEBOWITZ, C. GRAVEKAMP, H. A.    GHANBARI AND E. DADACHOVA (2017). “A Radiolabeled Fully Human    Antibody to Human Aspartyl (Asparaginyl) beta-Hydroxylase Is a    Promising Agent for Imaging and Therapy of Metastatic Breast    Cancer.” Cancer Biother Radiopharm 32(2): 57-65.-   14. TONG, M., J. S. GAO, D. BORGAS AND S. M. DE LA MONTE (2013).    “Phosphorylation Modulates Aspartyl-(Asparaginyl)-beta Hydroxylase    Protein Expression, Catalytic Activity and Migration in Human    Immature Neuronal Cerebellar Cells.” Cell Biol (Henderson, Nev.)    6(2).-   15. WU, G., Z. MA, Y. CHENG, W. HU, C. DENG, S. JIANG, T. LI, F.    CHEN AND Y. YANG (2018). “Targeting Gas6/TAM in cancer cells and    tumor microenvironment.” Mol Cancer 17(1): 20.-   16. YANG, H., K. SONG, T. XUE, X. P. XUE, T. HUYAN, W. WANG AND H.    WANG (2010). “The distribution and expression profiles of human    Aspartyl/Asparaginyl beta-hydroxylase in tumor cell lines and human    tissues.” Oncol Rep 24(5): 1257-1264.-   17. YEUNG, Y. A., A. H. FINNEY, I. A. KOYRAKH, M. S. LEBOWITZ, H. A.    GHANBARI, J. R. WANDS AND K. D. WITTRUP (2007). “Isolation and    characterization of human antibodies targeting human aspartyl    (asparaginyl) beta-hydroxylase.” Hum Antibodies 16(3-4): 163-176.-   18. DAHN, H., LAWENDEL, J. S., HOEGGER, E. F. ET AL (1954) “Über    eine neue Herstellung aromatisch substituierter Reduktone.”    Experientia 10: 245.-   19. PDB Full entry for 5JZZ; PFEFFER, T. KROJER, G. et al    ASPARTYL/ASPARAGINYL BETA-HYDROXYLASE (ASPH)OXYGENASE AND TPR    DOMAINS IN COMPLEX WITH MANGANESE, N-OXALYLGLYCINE AND FACTOR X    SUBSTRATE PEPTIDE FRAGMENT (TO BE PUBLISHED) M. A. Mcdonough, I.    Pfeffer, M. Munzel (May 17, 2016) “Aspartylasparaginyl    Beta-Hydroxylase (Asph)Oxygenase And Tp In Complex With Manganese,    N-Oxalylglycine And Cyclic Peptide Substrate Mimic Of Factor X” (No    publication in PubMed.) Crystal structure deposited as 5JZZ,    proteopedia.org/wiki/index.php/5jzz;    oca.weizmann.ac.il/oca-bin/ocashort?id=5JZZ; and    oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JZZ.-   20. TIMMINS, G. S. (2014) “Deuterated drugs: where are we now?”    Expert Opin. Ther. Patents 24{10}:1067-1075.

PATENT DOCUMENTS

-   U.S. Pat. No. 9,771,356.

What is claimed is:
 1. A deuterated compound of any one of formulas{I-A}, {I-B}, {I-C}, {I-D}, {I-E}, {I-F}, I-G}, or {I-H}:

or a salt, ester, metabolite, prodrug, or solvate thereof, wherein Ar¹is a substituted or unsubstituted C₆-C₂₀ aryl or 5-to 20-memberedheteroaryl; wherein at least one of V¹, V², V³, V⁴, V⁵, or Z¹, Z², Z³,Z⁴, Z⁵, Z⁶, Z⁷, Z⁸, or Z⁹ is a deuterium atom (D) and any atom notdesignated as deuterium is present as hydrogen (H, or not shown) at itsnatural isotopic abundance; wherein W is C(O), C(S), or S(O)₂; wherein Yis a single bond, O, CR⁵⁰R⁵¹, or NR⁵² when W is CO and W is a singlebond, CR⁵⁰R⁵¹ or NR⁵² when X is SO₂; wherein R⁵³ is selected from thegroup consisting of substituted or unsubstituted C₁-C₆ alkyl,substituted or unsubstituted C₂-C₆ alkenyl, substituted or unsubstitutedC₂-C₆ alkynyl, substituted or unsubstituted C₆-C₂₀ aryl, substituted orunsubstituted C₇-C₂₆ arylalkyl, substituted or unsubstituted 5 to20-membered heteroaryl, and substituted or unsubstituted 6-26 memberedheteroarylalkyl; and wherein Ar², designated as an unsubstituted orsubstituted C₆-C₂₀ heteroaryl is selected from the group consisting of:phenyl; naphthyl; pyridyl; pyridone; pyrimidine; pyradazine; pyrazine;purine; furan; thiophene; oxazole; thiazole; isoxazole; isothiazole;oxadiazole; thiadiazole; pyrrole; imidazole; triazole; tetrazole; anddiazepine.
 2. The deuterated compound of claim 1 having formula {I-A},

or a salt, ester, metabolite, prodrug, or solvate thereof, wherein V¹ isdeuterium (D) and any atom not designated as deuterium is present ashydrogen (H, or not shown) at its natural isotopic abundance.
 3. Thedeuterated compound of claim 1 having formula {I-B},

or a salt, ester, metabolite, prodrug, or solvate thereof, wherein atleast one of V¹, V², and V³ is a deuterium atom (D) and any atom notdesignated as deuterium is present as hydrogen (H, or not shown) at itsnatural isotopic abundance.
 4. The deuterated compound of claim 1 havingformula {I-C},

or a salt, ester, metabolite, prodrug, or solvate thereof, wherein atleast one of V¹, V², V³, or Z¹, Z², Z³, Z⁴, and Z⁵ is a deuterium atom(D) and any atom not designated as deuterium is present as hydrogen (H,or not shown) at its natural isotopic abundance.
 5. The deuteratedcompound of claim 1 having formula {I-D},

or a salt, ester, metabolite, prodrug, or solvate thereof, wherein atleast one of V⁴ or V⁵ is a deuterium atom (D) and any atom notdesignated as deuterium is present as hydrogen (H, or not shown) at itsnatural isotopic abundance.
 6. The deuterated compound of claim 1 havingformula {I-E},

or a salt, ester, metabolite, prodrug, or solvate thereof, wherein atleast one of V¹, V², V³, V⁴, or V⁵ is a deuterium atom (D) and any atomnot designated as deuterium is present as hydrogen (H, or not shown) atits natural isotopic abundance.
 7. The deuterated compound of claim 1having formula {I-F},

wherein at least one of V², V³, or Z¹, Z², Z³, Z⁴, or Z⁵ is a deuteriumatom (D) and any atom not designated as deuterium is present as hydrogen(H, or not shown) at its natural isotopic abundance.
 8. The deuteratedcompound of claim 1 having formula {I-G},

wherein at least one of V¹, V², V³, V⁴, V⁵, or Z¹, Z², Z³, Z⁴, Z⁵ is adeuterium atom (D) and any atom not designated as deuterium is presentas hydrogen (H, or not shown) at its natural isotopic abundance.
 9. Thedeuterated compound of claim 1 having formula {I-H},

wherein at least one of V², V³, Z²,Z³, Z⁴,Z⁵, Z⁶, Z⁸, or Z⁹ is adeuterium atom (D) and any atom not designated as deuterium is presentas hydrogen (H, or not shown) at its natural isotopic abundance.
 10. Thedeuterated compound of claim 1 having any one of formulas {I-A}, {I-B},{I-C}, {I-D}, {I-E}, {I-F}, {I-G}, wherein Ar¹ is a substituted C₆-C₂₀aryl group selected from the group consisting of one or moresubstituents selected from the group consisting of mono F, Cl, or Br atany position; difluoro or dichloro at different positions; mono and dimethyl any position; mono di and trifluoromethyl; mono and di OMe at anyposition; mono and di chlorophenyl at any position; CO₂Me; F and CO₂Me;CO₂Et; C(O)CH₃; C(O)NH₂; C(O):ND₂; COO⁻ND₂; COO⁻K⁺; [COO⁻]₂Mg⁺²;[COO⁻]₂Ca⁺²; mono and di CN at different positions; phenyl; CF₃; CO₃Me;CO₂D; CF₃; CO₂Me; benzo[d][1,3]dixol-5-yl; anddifluorobenzo[d][1,3]dixol-5-yl.
 11. The deuterated compound of claim 1having formula wherein R⁵³ is Ar², designated as an unsubstituted orsubstituted C₆-C₂₀ heteroaryl selected from the group consisting of:phenyl; naphthyl; pyridyl; pyridone; pyrimidine; pyradazine; pyrazine;purine; furan; thiophene; oxazole; thiazole; isoxazole; isothiazole;oxadiazole; thiadiazole; pyrrole; imidazole; triazole; tetrazole; anddiazepine.
 12. The deuterated compound of claim 1 having formula {I-A},wherein R⁵³ is a unsubstituted or substituted phenyl, selected from thegroup consisting of one or more substituents selected from the groupconsisting of: mono F, Cl, or Br at any position; difluoro or dichloroat different positions; mono and di methyl any position; mono di andtrifluoromethyl; mono and di OMe at any position; mono and dichlorophenyl at any position; CO₂Me; F and CO₂Me; CO₂Et; C(O)CH₃;C(O)NH₂; C(O):ND₂; COO⁻Na⁺; COO⁻K⁺; [COO⁻]₂Mg⁺²; [COO⁻]₂Ca⁺²; mono anddi CN at different positions; phenyl; CF₃; CO₃Me; CO₂D; CF₃; CO₂Me;benzo[d][1,3]dixol-5-yl; and difluorobenzo[d][1,3]dixol-5-yl.
 13. Thedeuterated compound of claim 1, wherein any atom not designated asdeuterium is present at its natural isotopic abundance, and where thepercentage of isotopic enrichment for each designated deuterium is atleast 50%.
 14. The deuterated compound of claim 13, wherein any atom notdesignated as deuterium is present at its natural isotopic abundance,and where the percentage of isotopic enrichment for each designateddeuterium is at least 75%.
 15. The deuterated compound of claim 14,wherein any atom not designated as deuterium is present at its naturalisotopic abundance, and where the percentage of isotopic enrichment foreach designated deuterium is at least 95%.
 16. The deuterated compoundof claim 15, wherein any atom not designated as deuterium is present atits natural isotopic abundance, and where the percentage of isotopicenrichment for each designated deuterium is at least 99%.
 17. Thedeuterated compound of claim 1, selected from the group consisting of2001 2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dmethanesulfonate-d3; 2001(R)(R)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dmethanesulfonate-d3; 2001(S)(S)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dmethanesulfonate-d3; 20022-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dethane-1-sulfonate-1,1-d2; 2002(R)(R)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dethane-1-sulfonate-1,1-d2; 2002(S)(S)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dethane-1-sulfonate-1,1-d2; 20032-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dpropane-1-sulfonate-1,1-d2; 2003(R)(R)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dpropane-1-sulfonate-1,1-d2; 2003(S)(S)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dpropane-1-sulfonate-1,1-d2; 20042-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dpropane-2-sulfonate-2-d; 2004(R)(R)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dpropane-2-sulfonate-2-d; 2004(S)(S)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dpropane-2-sulfonate-2-d; 20052-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dbutane-1-sulfonate-1,1-d2; 2005(R)(R)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dbutane-1-sulfonate-1,1-d2; 2005(S)(S)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dbutane-1-sulfonate-1,1-d2; 20062-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d2-methylpropane-1-sulfonate-1,1-d2; 2006(R)(R)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d2-methylpropane-1-sulfonate-1,1-d2; 2006(S)(S)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-d2-methylpropane-1-sulfonate-1,1-d2; 20072-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dbenzenesulfonate; 2007(R)(R)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dbenzenesulfonate; 2007(S)(S)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dbenzenesulfonate; 20082-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2008(R)(R)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2008(S)(S)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20092-amino-5-(2-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2009(R)(R)-2-amino-5-(2-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2009(S)(S)-2-amino-5-(2-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20102-amino-5-(3-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2010(R)(R)-2-amino-5-(3-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2010(S)(S)-2-amino-5-(3-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20112-amino-5-(2,3-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2011(R)(R)-2-amino-5-(2,3-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2011(S)(S)-2-amino-5-(2,3-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20122-amino-5-(2,4-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2012(R)(R)-2-amino-5-(2,4-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2012(S)(S)-2-amino-5-(2,4-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20132-amino-5-(2,5-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2013(R)(R)-2-amino-5-(2,5-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2013(S)(S)-2-amino-5-(2,5-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20142-amino-5-(3,4-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2014(R)(R)-2-amino-5-(3,4-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2014(S)(S)-2-amino-5-(3,4-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20152-amino-5-(3,5-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2015(R)(R)-2-amino-5-(3,5-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2015(S)(S)-2-amino-5-(3,5-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2016 methyl3-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2016(R) methyl(R)-3-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2016(S) methyl(S)-3-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2017 methyl4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2017(R) methyl(R)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2017(S) methyl(S)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2018 methyl4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;2018(R) methyl(R)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;2018(S) methyl(S)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;2019 ethyl4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2019(R) ethyl(R)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2019(S) ethyl(S)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2020 5-(4-acetylphenyl)-2-amino-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2020(R) (R)-5-(4acetylphenyl)-2-amino-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2020(S) (S)-5-(4acetylphenyl)-2-amino-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20212-amino-5-(4-carbamoylphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2021(R) (R)-2-amino-5-(4carbamoylphenyl)-4-oxo-4,5 dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2021(S) (S)-2-amino-5-(4carbamoylphenyl)-4-oxo-4,5 dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20224-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoicacid-d; 2022(R)(R)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoicacid-d; 2022(S)(S)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoicacid-d; 2023 sodium4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2023(R) sodium(R)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2023(S) sodium(S)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2024 potassium4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2024(R) potassium(R)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2024(S) potassium(S)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2027 2-amino-5-(2 fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2027(R)(R)-2-amino-5-(2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2027(S)(S)-2-amino-5-(2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20282-amino-5-(3-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2028(R)(R)-2-amino-5-(3-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2028(S)(S)-2-amino-5-(3-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20292-amino-5-(4-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2029(R)(R)-2-amino-5-(4-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2029(S)(R)-2-amino-5-(4-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20302-amino-5-(2,3-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2030(R)(R)-2-amino-5-(2,3-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2030(S)(S)-2-amino-5-(2,3-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20312-amino-5-(2,4-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2031(R)(R)-2-amino-5-(2,4-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2031(S)(S)-2-amino-5-(2,4-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20322-amino-5-(2,5-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2032(R)(R)-2-amino-5-(2,5-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2032(S)(S)-2-amino-5-(2,5-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20332-amino-5-(2,6-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2033(R)(R)-2-amino-5-(2,6-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2033(S)(S)-2-amino-5-(2,6-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20342-amino-5-(3,4-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2034(R)(R)-2-amino-5-(3,4-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2034(S)(S)-2-amino-5-(3,4-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20352-amino-5-(3,5-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2035(R)(R)-2-amino-5-(3,5-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2035(S)(S)-2-amino-5-(3,5-difluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20362-amino-5-(2-methoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2036(R)(R)-2-amino-5-(2-methoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2036(S)(S)-2-amino-5-(2-methoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20372-amino-5-(3-methoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2037(R)(R)-2-amino-5-(3-methoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2037(S)(S)-2-amino-5-(3-methoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20382-amino-5-(4-methoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2038(R)(R)-2-amino-5-(4-methoxyphenyl)-4-oxo-4,5 dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2038(S)(S)-2-amino-5-(4-methoxyphenyl)-4-oxo-4,5 dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20392-amino-5-(2,3-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2039(R)(R)-2-amino-5-(2,3-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2039(S)(S)-2-amino-5-(2,3-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20402-amino-5-(2,4-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2040(R)(R)-2-amino-5-(2,4-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2040(S)(S)-2-amino-5-(2,4-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20412-amino-5-(2,5-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2041(R)(R)-2-amino-5-(2,5-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2041(S)(S)-2-amino-5-(2,5-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20422-amino-5-(2,6-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2042(R)(R)-2-amino-5-(2,6-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2042(S)(S)-2-amino-5-(2,6-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20432-amino-5-(3,4-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2043(R)(S)-2-amino-5-(3,4-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2043(S)(R)-2-amino-5-(3,4-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20442-amino-5-(3,5-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2044(R)(R)-2-amino-5-(3,5-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2044(S)(S)-2-amino-5-(3,5-dimethoxyphenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20452-amino-5-(2-bromophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2045(R)(R)-2-amino-5-(2-bromophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2045(S)(S)-2-amino-5-(2-bromophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20462-amino-5-(3-bromophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2046(R)(R)-2-amino-5-(3-bromophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2046(S)(S)-2-amino-5-(3-bromophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20472-amino-5-(4-bromophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2047(R)(R)-2-amino-5-(4-bromophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2047(S)(S)-2-amino-5-(4-bromophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20482-amino-5-(2-chloro-3-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2048(R)(R)-2-amino-5-(2-chloro-3-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2048(S)(S)-2-amino-5-(2-chloro-3-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20492-amino-5-(2-chloro-4-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2049(R)(R)-2-amino-5-(2-chloro-4-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2049(S)(S)-2-amino-5-(2-chloro-4-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20502-amino-5-(2-chloro-5-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2050(R)(R)-2-amino-5-(2-chloro-5-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2050(S)(S)-2-amino-5-(2-chloro-5-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20512-amino-5-(2-chloro-6-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2051(R)(R)-2-amino-5-(2-chloro-6-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2051(S)(S)-2-amino-5-(2-chloro-6-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20522-amino-5-(3-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2052(R)(R)-2-amino-5-(3-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2052(S)(S)-2-amino-5-(3-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20532-amino-5-(3-chloro-4-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2053(R)(R)-2-amino-5-(3-chloro-4-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2053(S)(S)-2-amino-5-(3-chloro-4-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20542-amino-5-(3-chloro-5-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2054(R)(R)-2-amino-5-(3-chloro-5-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2054(S)(S)-2-amino-5-(3-chloro-5-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20552-amino-5-(5-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2055(R)(R)-2-amino-5-(5-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2055(S)(S)-2-amino-5-(5-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20562-amino-5-(4-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2056(R)(R)-2-amino-5-(4-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2056(S)(S)-2-amino-5-(4-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20572-amino-5-(4-chloro-3-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2057(R)(R)-2-amino-5-(4-chloro-3-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2057(S)(S)-2-amino-5-(4-chloro-3-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20582-amino-4-oxo-5-(o-tolyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2058(R)(R)-2-amino-4-oxo-5-(o-tolyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2058(S)(S)-2-amino-4-oxo-5-(o-tolyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20592-amino-4-oxo-5-(m-tolyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2059(R)(R)-2-amino-4-oxo-5-(m-tolyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2059(S)(S)-2-amino-4-oxo-5-(m-tolyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20602-amino-4-oxo-5-(p-tolyl)-4,5-dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2; 2060(R)(R)-2-amino-4-oxo-5-(p-tolyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2060(S)(S)-2-amino-4-oxo-5-(p-tolyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2061 2-amino-5-(3-cyanophenyl)-4-oxo-4,5dihydrofuran-3-yl-5-d phenylmethanesulfonate-d2; 2061(R)(R)-2-amino-5-(3-cyanophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2061(S)(S)-2-amino-5-(3-cyanophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20622-amino-5-(4-cyanophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2062(R)(R)-2-amino-5-(4-cyanophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2062(S)(S)-2-amino-5-(4-cyanophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20632-amino-4-oxo-5-phenyl-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2063(R)(R)-2-amino-4-oxo-5-phenyl-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2063(S)(S)-2-amino-4-oxo-5-phenyl-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20642-amino-4-oxo-5-(2-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2064(R)(R)-2-amino-4-oxo-5-(2-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2064(S)(S)-2-amino-4-oxo-5-(2-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20652-amino-4-oxo-5-(3-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2065(R)(R)-2-amino-4-oxo-5-(3-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2065(S)(S)-2-amino-4-oxo-5-(3-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20662-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2066(R)(R)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2066(S)(S)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20672-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d(4-fluorophenyl)methanesulfonate-d2; 2067(R)(R)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d(4-fluorophenyl)methanesulfonate-d2; 2067(S)(S)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d(4-fluorophenyl)methanesulfonate-d2; 2068 methyl4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)benzoate;2068(R) methyl(R)-4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)benzoate;2068(S) methyl(S)-4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)benzoate;2069 ethyl4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)benzoate;2069(R) ethyl(R)-4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)benzoate;2069(S) ethyl(S)-4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)benzoate;20704-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)benzoicacid-d; 2070(R) (R)4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)benzoicacid-d; 2070(S) (S)4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)benzoicacid-d; 2071 methyl4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;2071(R) methyl(R)-4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;2071(S) methyl(S)-4-(5-amino-4-((((4-fluorophenyl)methyl-d2)sulfonyl)oxy)-3-oxo-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;20722-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d(phenyl-d5)methanesulfonate-d2; 2072(R)(R)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5dihydrofuran-3-yl-5-d (phenyl-d5)methanesulfonate-d2; 2072(S)(S)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d(phenyl-d5)methanesulfonate-d2; 2073 methyl4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2073(R) methyl(R)-4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2073(S) methyl(S)-4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2074 ethyl4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2074(R) ethyl(R)-4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2074(S) ethyl(S)-4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;20754-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofura-2-yl-2-d)benzoicacid-d; 2075(R) (R)4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoicacid-d; 2075(S) (S)4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoicacid-d; 2076 methyl4-(5-amino-3-oxo-4-((((phenyl-d5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;2076(R) methyl (R)-4-(5-amino-3-oxo-4-((((phenyld5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;2076(S) methyl (S)-4-(5-amino-3-oxo-4-((((phenyld5)methyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;20772-amino-5-(benzo[d][1,3]dioxol-5-yl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2077(R)(R)-2-amino-5-(benzo[d][1,3]dioxol-5-yl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2077(S)(S)-2-amino-5-(benzo[d][1,3]dioxol-5-yl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20782-amino-5-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2078(R)(R)-2-amino-5-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2078(S)(S)-2-amino-5-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2079 methyl2-(4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)phenyl)acetate-d2;2079(R) methyl(R)-2-(4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)phenyl)acetate-d2;2079(S) methyl(S)-2-(4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)phenyl)acetate-d2;2080 2-amino-5-(4-(carbamoyl-d2)phenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2080(R)(R)-2-amino-5-(4-(carbamoyl-d2)phenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2080(S)(S)-2-amino-5-(4-(carbamoyl-d2)phenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20812-amino-4-oxo-5-(6-(trifluoromethyl)pyridin-3-yl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2081(R)(R)-2-amino-4-oxo-5-(6-(trifluoromethyl)pyridin-3-yl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2081(S)(S)-2-amino-4-oxo-5-(6-(trifluoromethyl)pyridin-3-yl-)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20822-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d(4-chlorophenyl)methanesulfonate-d2;2082(R)(R)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d(4-chlorophenyl)methanesulfonate-d2; 2082(S)(S)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d(4-chlorophenyl)methanesulfonate-d2; 20832-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d(4-(trifluoromethyl)phenyl)methanesulfonate-d2; 2083(R)(R)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d(4-(trifluoromethyl)phenyl)methanesulfonate-d2; 20842-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-phenylmethanesulfonate;20852-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2085(R)(R)-2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2085(S)(S)-2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20862-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-(phenyl-d5)methanesulfonate;20872-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d(phenyl-d5)methanesulfonate-d2; 2087(R)(R)-2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d(phenyl-d5)methanesulfonate-d2; 2087(S)(S)-2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-d(phenyl-d5)methanesulfonate-d2; 20882-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-phenylmethanesulfonate;20892-amino-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2089(R)(R)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2089(S)(S)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20902-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5d phenylmethanesulfonate-d2; 2090(R)(R)-2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2090(S)(S)-2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20912-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-(phenyl-d5)methanesulfonate;20922-amino-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d(phenyl-d5)methanesulfonate-d2; 2092(R)(R)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d(phenyl-d5)methanesulfonate-d2; 2092(S)(S)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d(phenyl-d5)methanesulfonate-d2; 20932-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d(phenyl-d5)methanesulfonate-d2; 2093(R)(R)-2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6-d4)-4,5-dihydrofuran-3-yl-5-d(phenyl-d5)methanesulfonate- d2; and 2093(S)(S)-2-(amino-d2)-4-oxo-5-(4-(trifluoromethyl)phenyl-2,3,5,6d4)-4,5-dihydrofuran-3-yl-5-d (phenyl-d5)methanesulfonate-d2.


18. The deuterated compound of claim 3, having formula {I-B}.
 19. Thedeuterated compound of claim 18, wherein Ar² is phenyl, and Ar² is asubstituted C₆-C₂₀ aryl group selected from the group consisting of oneor more substituents selected from the group consisting of mono F, Cl,or Br at any position; difluoro or dichloro at different positions; monoand di methyl any position; mono di and trifluoromethyl; mono and di OMeat any position; mono and di chlorophenyl at any position; CO₂Me; F andCO₂Me; CO₂Et; C(O)CH₃; C(O)NH₂; C(O):ND₂; COO⁻Na⁺; COO⁻K⁺; [COO⁻]₂Mg⁺²;[COO⁻]₂Ca⁺²; mono and di CN at different positions; phenyl; CF₃; CO₃Me;CO₂D; CF₃; CO₂Me; benzo[d][1,3]dixol-5-yl; anddifluorobenzo[d][1,3]dixol-5-yl.
 20. The deuterated compound of claim19, selected from the group consisting of 20082-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2008(R)(R)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2008(S)(S)-2-amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20142-amino-5-(3,4-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2014(R)(R)-2-amino-5-(3,4-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2014(S)(S)-2-amino-5-(3,4-dichlorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2017 methyl4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2017(R) methyl(R)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2017(S) methyl(S)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2018 methyl4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;2018(R) methyl(R)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;2018(S) methyl(S)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)-2-fluorobenzoate;2019ethyl-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2019(R) ethyl(R)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2019(S) ethyl(S)-4-(5-amino-3-oxo-4-(((phenylmethyl-d2)sulfonyl)oxy)-2,3-dihydrofuran-2-yl-2-d)benzoate;2052 2-amino-5-(3-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2052(R)(R)-2-amino-5-(3-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2052(S)(S)-2-amino-5-(3-chloro-2-fluorophenyl)-4-oxo-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 20662-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; 2066(R)(R)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2; and 2066(S)(S)-2-amino-4-oxo-5-(4-(trifluoromethyl)phenyl)-4,5-dihydrofuran-3-yl-5-dphenylmethanesulfonate-d2.


21. A pharmaceutical composition comprising a compound of claim 1 or apharmaceutical acceptable salt thereof and a pharmaceutically-acceptablecarrier.
 22. A pharmaceutical composition comprising a compound of claim1 or a pharmaceutical acceptable ester, metabolite, prodrug, or solvatethereof and a pharmaceutically-acceptable carrier.
 23. A pharmaceuticalcomposition comprising a compound of claim 17 or a pharmaceuticalacceptable salt thereof and a pharmaceutically-acceptable carrier.
 24. Apharmaceutical composition comprising a compound of claim 17 or apharmaceutical acceptable ester, metabolite, prodrug, or solvate thereofand a pharmaceutically-acceptable carrier.
 25. A method of preparing adeuterated compound of claim 1 having any of formulas {I-A, I-B, I-C,I-F} by contacting an undeuterated precursor compound with a suitablebase and a deuterated solvent.
 26. The method of claim 25, wherein saidsuitable base is selected from the group consisting of LiOD, NaOD, KOD,CsOD, Ba(OD)₂, Ca(OD)₂, Mg(OD)₂, Mn(OD)₂, Li₂CO₃, Na₂CO₃, K₂CO₃, Cs₂CO₃,MgCO₃, and CaCO₃.
 27. The method of claim 25, wherein said deuteratedsolvent is D₂O.
 28. A method of treating one or more conditionsassociated with a proliferative cellular disorder, wherein saidconditions associated with a proliferative cellular disorder is selectedfrom the group consisting of cancer, pancreatic cancer, lung cancer,breast cancer, glioblastoma multiform, neuroblastoma, osteosarcoma,ovarian cancer, cervical cancer, head and neck cancer,cholangiocarcinoma, and hepatocellular carcinoma, by administering oneor more doses of a pharmaceutical composition comprising one or morecompounds of claim 1 in one or more amounts effective to treat one ormore conditions associated with the proliferative cellular disorder.